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. 2025 Jun 30;30(3):250–262. doi: 10.3746/pnf.2025.30.3.250

Association of Lutein with Cancer: A Systematic Review of the Lutein Effects on Cellular Processes Involved in Cancer Progression

Fahmideh Bagrezaei 1,2, Sorayya Kheirouri 1,✉, Mohammad Alizadeh 1,✉
PMCID: PMC12213252  PMID: 40612761

Abstract

Lutein belongs to the carotenoid family of xanthophylls, which have antioxidant, anti-inflammatory, and anticancer properties. This study aimed to comprehensively review the interactions between lutein and critical cellular processes that influence cancer progression. A search of electronic databases, including PubMed, Science Direct, Cochrane Library, Web of Science, Scopus, Google Scholar, and Google, was conducted for the keywords “cancer or tumor or neoplasm or carcinoma” and “lutein” in the titles or abstracts of published research. A total of 47 studies were reviewed, and it was shown that lutein reduced estrogen receptors (2 out of 4 studies), DNA damage (4 out of 8 studies), cancer cell survival (1 out of 1 studies), growth (7 out of 7 studies), and proliferation (19 out of 19 studies) as well as cancer cell invasion, migration, metastasis, and adhesion (2 out of 2 studies), but induced apoptosis (17 out of 17 studies) and cell differentiation (1 out of 1 studies). According to this review, lutein may be effective in suppressing cellular processes involved in cancer progression through a variety of mechanisms.

Keywords: cancerization, cell physiological phenomena, lutein, neoplasms

INTRODUCTION

Cancer is a significant health problem at the global scale. In 2020, there was approximately 19.3 million new cases of cancer worldwide, and approximately 10 million people deaths from this condition (Sung et al., 2021). It is well-established that certain foods or food ingredients can inhibit the growth of cancer cells. Hence, natural food compounds are currently widely used as an alternative therapeutic strategy for treating cancer as well as various chronic diseases, as they have fewer side effects (Gao et al., 2022).

Carotenoids are essential dietary components that play a role in the molecular and biochemical processes that lead to cancer cell death (Black et al., 2020). They are well-known for their antioxidant properties and involvement in the regulation of cell growth, immune response, and modulation of gene expression (Black et al., 2020). There are two types of carotenoids: carotenes (hydrocarbons like carotene and lycopene) and xanthophylls (polar compounds whose molecular structure includes oxygen atoms, like lutein and zeaxanthin) (Milani et al., 2017).

Human serum contains high levels of lutein, which is synthesized by plants (Demmig-Adams et al., 2020). A plentiful source of this substance can be found in eggs and dark green leafy vegetables (Gómez-García et al., 2021). Lutein accumulates in the macula and is responsible for vision (Abdel-Aal et al., 2013). In addition, it has recently gained public attention due to its potential to prevent degenerative eye disease and cancer (Brewczyński et al., 2021; Mitra et al., 2021). Epidemiological studies have shown that serum lutein levels are inversely related to the risk of cancer (Min and Min, 2014; Graff et al., 2017; Van Hoang et al., 2018). Research has shown that lutein, which is recognized for its superior antioxidant properties compared with other carotenoids, may play a significant role in cancer prevention, leading to increasing interest in its potential to also inhibit cancer progression in recent years (Murillo et al., 2016; Gong et al., 2018; Zhang et al., 2018). So far, numerous studies have investigated the effectiveness of lutein against various cancers, and it seems necessary to conduct a systematic review of the available evidence to provide conclusive information as a basis for making decisions on the use of this compound in cancer prevention or treatment. This systematic review aimed to comprehensively evaluate the association between lutein and cancer by examining the cellular processes that may be effectively influenced by this bioactive compound and, specifically, the underlying mechanisms involved.

MATERIALS AND METHODS

Literature search and eligible articles

A literature search of the PubMed, Google Scholar, Science Direct, Cochrane Library, Web of Science, Scopus databases, and Google was conducted without time restrictions on March 29, 2023. The terms searched in the titles or abstracts of published research were “cancer or tumor or neoplasm or carcinoma” and “lutein” (Supplementary Table 1). Only original, full-text journal articles written in English that examined the relationship between lutein and cancer and specifically focused on lutein, without including other carotenoids, were considered in this review. Review articles, conference papers, abstracts, editorials, and letters were excluded.

Selection of articles

The extracted articles were stored in an EndNote file, and duplicate reports were removed. The remaining titles and abstracts were reviewed to screen articles with the correct scope for the present review. The full texts of the screened articles were then separately and critically analyzed for eligibility. The process of searching and selecting articles was performed by two researchers separately. PICO/PECO (participant, intervention/exposure, comparison, outcome) approach for this review was as follows: Human or animals with cancer (any type), or cancer cell lines were defined as population; lutein treatment or dietary lutein intake was considered as intervention or exposure; comparator was healthy individuals (in human studies), healthy animals (in experimental studies), cells without treatment with lutein (in cellular studies); and outcomes were cancer development (any type of cancer) or activation/inhibition of cancer mechanistic pathways.

Data analysis

The data related to the participants’ characteristics, study design, cancer type, food intake assessment method, duration, and outcomes were extracted from studies that had been previously selected based on the PRISMA algorithm.

Ethical approval

This research has been approved by the ethics committee of Tabriz University of Medical Sciences (IR.TBZMED.REC.1401.519).

RESULTS

As shown in Fig. 1, a total of 2,552 articles were initially identified. Finally, after removing 1,662 unrelated and 833 duplicate articles as well as 10 non-accessible articles, only 47 studies (6 human, 34 cellular, and 7 animal studies) were retained for the present review. The human studies consisted of one nested case-control study, a case-control, two cohort studies, two cross-sectional studies. The studies were categorized according to the observed effects of lutein on various aspects of cancer progression, as reported below.

Fig. 1.

Fig. 1

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Flow chart of the systematic literature search and selection of studies based on the PRISMA flow diagram.

Estrogen receptors

Estrogen receptors (ERs) are a group of proteins found inside cells. There are two ERs in mammals, ERα and ERβ, both of which bind to the regulatory DNA sequences in specific target genes, regulating transcription. ERs are overexpressed in breast cancers and ER-mediated signaling is critical in the cancer initiation, progression, metastasis, and prognosis (Haldosén et al., 2014).

Among the examined studies, four evaluated the association between dietary lutein and ERs in breast cancer. More specifically, a nested case-control study of 1,502 patients showed that dietary lutein was not significantly associated with ERs (Bakker et al., 2016), while a cohort study of 3,564 patients revealed an inverse association between dietary lutein and ERs (Bitsie et al., 2021). The latter result was also obtained in a case-control study of 1,463 patients (Gaudet et al., 2004). Finally, a cross-sectional study of 142 patients, showed that plasma lutein concentrations were associated with the risk of ER-positive breast cancer (Rock et al., 1996). These conflicting results suggest that the relationship between dietary lutein and ERs needs to be further investigated.

DNA damage

Eight studies have investigated the association between lutein and DNA damage. Of these, four found that lutein exerted a protective effect. Two of the eight studies were conducted on humans and are shown in Table 1. The first was a cross-sectional study of 20 breast cancer patients, revealed that dietary lutein was not significantly associated with protection against DNA damage (Mousseau et al., 2005), while the second was a cohort study of 405 patients with prostate cancer, reported no protective effects at all (Woelfelschneider et al., 2008).

Table 1.

List of the human studies included in this review and related information

Citation Study design Country Type of cancer Participant/sex Mean age (years) Follow-up time Food intake assessment tool Major confounders Findings
Estrogen receptors
Bakker et al., 2016 Nested case-control 10 European countries Breast Case: n=1,502 Control: n=1,502/Female Cases: 49.98±8.58 Controls: 50.00±8.59 Not applicable Not stated Lifestyle behaviors and genetic availability of bioactive compounds There was no association between lutein and ER (P-trend=0.23).
Bitsie et al., 2021 Nested case-control America Breast Case: n=3,564 Control: n=11,843/Female BWHS; cases: 53.4 (10.7), Controls: 52.5 (10.9), WCHS; case: 51.2 (10.3), Controls: 49.8 (9.8), MEC; cases: 68.4 (9.4), Controls: 67.8 (9.3), AMBER [cases: 56.4 (12.2), controls: 56.3 (12.5)] 10 years FFQ Age, education, BMI, family history of breast cancer, age at menarche, parity, age at first birth, menopausal status, hormone therapy use, duration of oral contraceptive use, smoking status, alcohol use, and total energy intake Lutein was associated with a lower risk of ER+ breast cancer (P-trend=0.020).
Gaudet et al., 2004 Case-control America Breast Case: n=1,463, Control: n=1,500/Female Case: <65
Control: 65		 Not applicable FFQ Menopausal status, smoking/alcohol consumption, family history of cancer, use of hormone replacement therapy and vitamin supplements, lactation, age at first birth, parity, BMI Lutein intake had an inverse association with ER in postmenopausal (P-trend=0.03).
Rock et al., 1996 Cross-sectional America Breast 142/Female >18 years 18 months FFQ Energy, demographic, and hormonal status ER-positive risk was associated with the intake of lutein (P<0.02).
DNA damage
Mousseau et al., 2005 Cross-sectional France Breast Case: n=20 Control: n=15/Female 54/35－65 Not applicable Not stated Not stated. Lutein did not protect against DNA damage (P=0.332).
Woelfelschneider et al. 2008 Cohort Heidelberg Prostate 405/Male 68±6.7 4 years Not stated Age, alcohol/tobacco consumption, and antioxidant plasma levels Lutein failed to protect against DNA damage (P=0.02).
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FFQ, Food-frequency questionnaire; ER, estrogen receptor; BWHS, black women’s health study; WCHS, women’s circle of health study; MEC, multiethnic cohort study; AMBER, African American breast cancer epidemiology and risk; BMI, body mass index.

Two studies were animal studies (Table 2). Both of them, one conducted on 36 and the other on 24 male Wistar rats with liver cancer, reported that lutein intake had a protective effect against DNA damage (Toledo et al., 2003; Moreno et al., 2007).

Table 2.

List of the animal studies included in this review and related information

Citation Country Type of animal Type of comorbidity Number of animals/Mean age (years) Intervention duration Dose of lutein Finding
DNA damage
Toledo et al., 2003 Brazil Male Wistar rats Liver cancer 36/− 8 weeks 70 mg/kg Lutein protected against DNA damage (P<0.05).
Moreno et al., 2007 Brazil Male Wistar rats Liver cancer 24/− 6 weeks 70 mg/kg DNA damage was prevented by lutein (P<0.05).
Survival and growth of cancer cells
Lee, 2008 Korea Male mice Leukemic cancer −/5-week-old 30 days 13 mg/kg for 30 days Lutein inhibited cell growth by inhibiting ROS (P<0.05).
Apoptosis
Reynoso-Camacho et al., 2011 Mexico Male Sprague-Dawley rats Colon cancer 78/4－5 weeks 8 weeks 0.002 % Lutein decreased several anti-apoptotic proteins via reduced protein expression of K-RAS, PKB/AKT, and β-catenin (P<0.001, P<0.05).
Cell proliferation
Kim et al., 1998 Japan Male mice Colon cancer 145/4-week-old 12 weeks 0.05% Lutein inhibited the proliferation of cells (P<0.01).
Cheng et al., 2007 Taiwan Male hamster Oral cancer 41/8-week-old 16 weeks 2.7 mg/mL Cell proliferation was prevented by lutein by lowering the expression of cyclin D (P<0.05).
Sindhu and Kuttan, 2013 India Male Wistar rats Cisplatin-induced nephropathy 32/− 29 weeks 50, 250 mg/kg body weight Lutein slowed the proliferation of cells by inhibiting ROS (P<0.001).
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ROS, reactive oxygen species; K-RAS, Kirsten rat sarcoma virus; PKB/AKT, protein kinase B/AK strain tranforming.

The remaining four were cellular studies (Table 3). Of these, two found that treatment with lutein protected against DNA damage (García-Gasca et al., 1998; Serpeloni et al., 2012) while the other two did not (Astley et al., 2002, 2004).

Table 3.

List of the cellular studies included in this review and related information

Citation Country Type of cancer cell Dose of lutein and intervention duration Finding
DNA damage
García-Gasca et al., 1998 Mexico Hepatocyte 1 µmol/L for 4 h DNA damage was protected by lutein (P≤0.05).
Astley et al., 2002 UK MOLT-17 8 µmol/L for 24 h Lutein did not protect against DNA damage via oxidative stress (P=0.08).
Astley et al., 2004 UK MOLT-17 0.00－8.00 mmol/L for 24 h Incubation with lutein increased the numbers of DNA single-strand breaks in control cells.
Serpeloni et al., 2012 Brazil HepG2 0, 0.1, 1, 5, 10, 25, 50, 100 µmol/L for 24 h DNA damage was protected by lutein (P≤0.05).
Survival and growth of cancer cells
Lu et al., 2005 America Prostate 8 µmol/L for 24 and 72 h Lutein inhibited cell growth by regulating CDK (P≤0.05).
Arunkumar et al., 2015 India HepG2 1, 5, 10, 20 µmol/L for 24, 48, and 72 h Lutein nanocapsules reduced cell growth (IC50 value, 10.9 µM).
Rafi et al., 2015 America Prostate 0, 1, 10, 25 µmol/L for 48 h Lutein affected the expression of critical genes associated with cell growth, including growth factors, CDK5, GSTP1, and PK (P<0.05, P<0.01, P<0.001).
Gong et al., 2018 America Breast 0.5－2 µmol/L for 48 h Lutein inhibited cell growth.
Kavalappa et al., 2021 India MCF-7, MDA-MB-231 1, 5, 10, 25 µmol/L for MCF-7 and 5, 10, 20, 30 µmol/L for MDA-MB-231 for 24 h Cell survival were inhibited by apoptosis induced by lutein through the ROS/NRF2/AKT/ERK/NF-κB pathway (P<0.05, P<0.01).
Sumantran et al., 2000 America SV40, MCF-7 7 µmol/L for 4 days Lutein reduced cell growth (P=0.002) through BCL-2 and Bax protein levels.
Zaini et al., 2012 UK CCRF-CEM, Jurkat, MOLT-3 0, 0.5, 5, 25, 50, 100 µmol/L for 24 h Lutein blocked cell growth (P≤0.05).
Apoptosis
Sumantran et al., 2000 America SV40, MCF-7 7 µmol/L for 4 days Lutein induced apoptosis (P=0.016) through Bcl-2 and Bax protein levels.
Müller et al., 2002 UK Human leukemic T-lymphoblast 20 µmol/L for 24 h Lutein induced apoptosis by activating Caspase-3 and modulating DNA damage (P≤0.001).
Molnár et al., 2004 Hungary Mouse lymphoma, human breast 2－20 µg/mL for 24 h Lutein (2%/mL) triggered apoptosis in human breast cancer cells (3.88%), and lutein (20 µg/mL) induced apoptosis in mouse lymphoma cells (0.35%).
Ugocsai et al., 2005 Hungary Colon 10 µg/mL for 24 h Lutein caused the activation of apoptosis (4.15－5.49%)
Cha et al., 2008 Korea HCT116 0, 20, 40, 60, 80, 100 µg/mL for 24 h Lutein induced apoptosis with IC50 of 21.02±0.85 µg/mL.
Tsai et al., 2010 Taiwan Hep3B 5, 10, 30, 50, 70, 100 µg/mL for 72 h Lutein induced apoptosis by regulating the cell cycle (P<0.05).
Zaini et al., 2012 UK
 CCRF-CEM, Jurkat, MOLT-3 0, 0.5, 5, 25, 50, 100 µmol/L for 24 h Lutein triggered apoptosis by controlling the cell cycle (P≤0.05).
Chang et al., 2013 Taiwan IEC-6 0, 0.1, 1, 2.5, 5, 10 µmol/L for 24 h Lutein induced apoptosis by regulating Caspase-3/ROS/BCL-2 (P<0.05).
Behbahani et al., 2014 Iran Breast 1/4 of CC50 for 6 and 12 h Lutein stimulated cell death by the expression levels of the P53, Caspase-3, and Bax genes (P<0.05).
Sowmya et al., 2015 India HeLa 25－100 µmol/L for 48 h Lutein induced apoptosis by decreasing ROS levels (P<0.05).
Vijay et al., 2016 India RAW264.7, HL-60 20 µmol/L for 12 h Lutein promoted apoptosis (P<0.05).
Yamagata et al., 2017 Japan Lung 0, 10, 30, or 50 µmol/L for 8 h Lutein induced apoptosis via increased Bax and decreased BCL-2 levels (P<0.05).
Gong et al., 2018 America Breast 0.5－2 µmol/L for 48 h Lutein induced apoptosis by decreasing BCL-2 and increasing Bax, P53 signaling (P<0.05).
Vijay et al., 2018 India Breast 0－50 µmol/L for 24 h Lutein changed the redox status, boosted oxidative stress-induced apoptosis, and elevated P53 and Bax expression (P<0.05).
Gansukh et al., 2019 Korea HeLa 1, 10 µmol/L for 24 and 48 h Lutein induced apoptosis by activating Bax and Caspase-3 (P<0.05).
Kavalappa et al., 2021 India MCF-7, MDA-MB-231 1, 5, 10, 25 µmol/L for MCF-7 and 5, 10, 20, 30 µmol/L for MDA-MB-231 for 24 h Apoptosis induced by lutein through the ROS/NRF2/AKT/ERK/NF-κB pathway (P<0.05, P<0.01).
Cell proliferation
Gross et al., 1997 America Leukemia 0.1, 1, 10 µmol/L on days 3, 5, and 7 Lutein reduced cell proliferation rates by inhibiting oxidative stress (P<0.05).
Lu et al., 2005 America Prostate 8 µmol/L for 24 and 72 h Lutein inhibited cell proliferation by regulating CDK (P≤0.05).
Cheng et al., 2007 Taiwan KB 5, 10, 20, 30 µmol/L for 24 h Lutein inhibited cell proliferation by suppressing the expression of PCNA and cyclin D (P<0.05).
Gunasekera et al., 2007 America Prostate 2.0 µmol/L on 4 days Lutein inhibited cell proliferation (P<0.05).
Sun and Yao, 2007 China KB 20, 30, 40, 50 µmol/L for 24, 48, and 72 h Lutein inhibited cell proliferation by reducing oxidative stress (P<0.05).
Cha et al., 2008 Korea HCT116 0, 20, 40, 60, 80, 100 µg/mL for 24 h Lutein induced antiproliferative activity of HCT116 with IC50 of 21.02±0.85 µg/mL.
Tsai et al., 2010 Taiwan Hep3B 5, 10, 30, 50, 70, 100 µg/mL for 72 h Lutein inhibited proliferation (P<0.05).
Rafi et al., 2015 America Prostate 0, 1, 10, 25 µmol/L for 48 h Lutein affected the expression of critical genes associated with cell proliferation, including growth factors, CDK5, GSTP1, and PK (P<0.05, P<0.01, P<0.001).
Vijay et al., 2016 India RAW264.7, HL-60 20 µmol/L for 12 h Lutein inhibited proliferation by reducing toxicity and inflammation (P<0.05).
Castro-Puyana et al., 2017 Spain Colon 27, 83, or 250 µg/mL for 24 h Lutein inhibited cell proliferation (P<0.05).
Chang et al., 2018 China T47D 0, 6.25, 12.5, 25, 50 µg/mL for 24, 48, and 72 h Lutein inhibited cell proliferation and ROS by inhibiting the NF-κB and activating the NRF2/ARE (P<0.05, P<0.01).
Li et al., 2018 China MDA-MB-157, MCF-7 0, 5, 10, 20, 40, 80, 120 µmol/L for 24 h Lutein inhibited cell proliferation by inhibiting the HIF-1α/Notch signaling pathway (P<0.01).
Campestrini et al., 2019 Brazil MCF-7, NCI-H460, HeLa, and HepG2 100, 200, 400 µg/mL Lutein inhibited cell proliferation by suppressing ROS (GI50 for MCF-7=0.10, NCI-H460=0.43, HeLa=0.25, and HepG2=—0.53)
Kavalappa et al., 2021 India MCF-7, MDA-MB-231 1, 5, 10, 25 µmol/L for MCF-7 and 5, 10, 20, 30 µmol/L for MDA-MB-231 for 24 h Cell proliferation was inhibited by apoptosis induced by lutein through the ROS/NRF2/AKT/ERK/NF-κB pathway (P<0.05).
Omar et al., 2021 Egypt MCF-7, HepG2, A549 HCT116, PC3, HFB4 IC50% for 24 h Lutein inhibited cell proliferation in breast MCF-7 (IC50, 3.10±0.47 µg/mL) and liver HepG2 (IC50, 6.11±0.84 µg/mL) cells.
Zhang et al., 2021 China MCF-7, T47D 0, 6.25, 12.50, 25.00, 50.00 µg/mL for 24 h Increased levels of miR-590-3p enhanced lutein's effectiveness in inhibiting proliferation (P<0.05).
Cancer cell invasion, migration, metastasis, and adhesion
Chen et al., 2015 Taiwan SK-Hep-1 0.4 or 0.5 µmol/L for 24 and 48 h Lutein inhibited migration, invasion, metastasis, and adhesion by inhibiting MMP-2 (P<0.05).
Li et al., 2018 China MDA-MB-157, MCF7 0, 5, 10, 20, 40, 80, 120 µmol/L for 24 h Lutein inhibited cell invasion and migration by inhibiting the HIF-1α/Notch signaling pathway (P<0.05).
Cell differentiation
Gross et al., 1997 America Leukemia 0.1, 1, 10 µmol/L on days 3, 5, and 7 Lutein promoted cell differentiation (P<0.05).
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MOLT, Minowaad’s original lympholastic T-cell; MCF, Michigan cancer foundation; MDA-MB, M.D.Anderson-metastatic breast cancer; IC50, inhibitory concentration 50%; NF-κB, nuclear Kappa-light-chain enhancer of activated B-cell; SV40, simian virus 40; CCRF-CEM, human T lymphoblasts; Bax, BCL-2 associated protein X; CC50, concentration of cytotoxicity at 50%; NCI-H460, non-small cell lung cancer cell line; HCT, human colorectal tumor; HepG2, human epithelial liver G2; PC, prostate cancer; HFB4, human fibroblast cell line 4; Hep3B, human epithelial liver 3B; RAW264.7, mouse marcrophage cell line; T47D, isolated from invasive ductal carcinoma of breast; SK-Hep-1, immortal, human hepatic adenocarcinoma cell line; Hep-1, human epithelial liver 1; KB cell, a human oral epidermoid carcinoma cell line; Hep G2, human hepatocyte carcinoma cells; GSTP1, glutathione Stransferase Pi 1; PCNA, proliferating cell nuclear antigen; MMP, matrix metalloproteinase; ROS, reactive oxygen species; CDK, cyclin-dependent kinase; ERKs, extracellular signal-regulated kinases; NRF2, Nucleus erythroid factor 2; HIF, hypoxia-inducible factors; BCL-2, B-cell lymphoma; PK, protein kinase; mirRNAs, microRNAs; Notch, neurogenic locus notch homolog protein; ARE, nucleus’s antioxidant response element; HL-60, human promyelocytic leukemia cell line.

Overall, these contrasting results with regard to the relationship between lutein and DNA damage underscore the need for further investigation.

Survival and growth of cancer cells

Only one animal study (Table 2) investigated the effect of lutein on cell growth and reported an inhibitory action in male mice treated with this compound at a concentration of 13 mg/kg (Lee, 2008). Six cellular studies investigated the effect of lutein on cancer cell growth (Table 3). All revealed an inhibitory action (Sumantran et al., 2000; Lu et al., 2005; Zaini et al., 2012; Arunkumar et al., 2015; Rafi et al., 2015; Gong et al., 2018). One cellular study assessed the effect of lutein on cancer cell survival, and reported an inhibitory action (Kavalappa et al., 2021). Altogether, these findings suggest that lutein may effectively inhibit cancer cell growth and survival.

Apoptosis

As shown in Table 2, only one animal study investigated the effect of lutein on apoptosis inhibitory proteins and found that their levels were reduced after treatment (Reynoso-Camacho et al., 2011). A total of 16 cellular studies (Table 3) investigated the effect of lutein on apoptosis in cancer cells, and all of them found a promoting effect (Sumantran et al., 2000; Müller et al., 2002; Molnár et al., 2004; Ugocsai et al., 2005; Cha et al., 2008; Tsai et al., 2010; Zaini et al., 2012; Chang et al., 2013; Behbahani, 2014; Sowmya et al., 2015; Vijay et al., 2016; Yamagata et al., 2017; Gong et al., 2018; Vijay et al., 2018; Gansukh et al., 2019; Kavalappa et al., 2021).

Overall, these studies suggest that lutein reduces the levels of apoptosis inhibitory proteins and increases apoptosis in cancer cells, which is indicative of its potential anticancer effects.

Cell proliferation

As shown in Table 2, three animal studies investigated the effect of lutein on cell proliferation, all of which reported an inhibitory action (Kim et al., 1998; Cheng et al., 2007; Sindhu and Kuttan, 2013). A total of 16 cellular studies investigated the effect of lutein on the proliferation of cancer cells (Table 3), and all of them indicated that treatment with this compound inhibited proliferation (Gross et al., 1997; Lu et al., 2005; Cheng et al., 2007; Gunasekera et al., 2007; Sun and Yao, 2007; Cha et al., 2008; Tsai et al., 2010; Rafi et al., 2015; Vijay et al., 2016; Castro-Puyana et al., 2017; Chang et al., 2018; Li et al., 2018; Campestrini et al., 2019; Kavalappa et al., 2021; Omar et al., 2021; Zhang et al., 2021). Taken together, these results suggest that lutein inhibits the proliferation of cancer cells.

Cancer cell invasion, migration, metastasis, and adhesion

As shown in Table 3, two cellular studies investigated the effect of lutein on cancer cell migration, invasion, metastasis, and adhesion. One of them was a survey of human breast cancer cell lines (MDA-MB-157 and MCF-7) showing that treatment with lutein inhibited cell migration and invasion (Li et al., 2018). The other, a study of human hepatocarcinoma cells, found that administering lutein to the cells inhibited their migration, invasion, metastasis, and adhesion (Chen et al., 2015). Overall, these findings suggest that lutein treatment may suppress the above-mentioned processes related to cancer progression.

Cell differentiation

As shown in Table 3, only one study investigated the effect of lutein on cell differentiation and found that treatment with this compound had a promoting effect (Gross et al., 1997).

DISCUSSION

The review of the 47 selected studies showed that treatment with lutein reduced ERs (2 out of 4 studies), DNA damage (4 out of 8 studies), cancer cell survival (1 out of 1 studies), growth (7 out of 7 studies), proliferation (19 out of 19 studies) as well as cancer cell invasion, migration, metastasis, and adhesion (2 out of 2 studies), but induced apoptosis (17 out of 17 studies), and cell differentiation (1 out of 1 study).

With regard to the involvement of lutein in cancer development and progression, the findings are still uncertain. Based on evidence, oxidative stress associated with free radicals can harm DNA, causing strand breaks and base changes that disrupt gene function, leading to mutations or cancer (Jomova et al., 2023). It also activates cell death pathways and impairs vital processes, contributing to tissue dysfunction and conditions such as cancer, neurodegeneration, and cardiovascular disease (Chavda et al., 2022). Moreover, prolonged oxidative stress can worsen inflammation, causing damaged cells to release pro-inflammatory mediators that harm nearby healthy cells. This can lead to genetic mutations that disrupt cell cycle regulation and apoptosis, promoting uncontrolled cell growth and tumor formation (Kawahara et al., 2022; Zhang et al., 2023). In addition, oxidative stress activates cell signaling pathways, promoting cancer cell migration and invasion (Iqbal et al., 2024). These events have also been observed in the presence of inflammatory cells in the tumor microenvironment (Neophytou et al., 2021; Shi et al., 2024). According to scientific research, lutein’s antioxidant and anti-inflammatory properties may play a role in reducing oxidative stress, inflammation, and apoptosis, which in turn would inhibit cancer progression.

The possible mechanistic signaling pathways through which lutein reduces oxidative stress, inflammation, and apoptosis are shown in Fig. 2 and described below.

Fig. 2.

Fig. 2

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Inhibitory or activating effect of lutein on cellular processes involved in cancer development. NF-κB, including factor kappa B; ERK, extracellular signal-regulated kinases; NRF2, nucleus erythroid factor 2; HIF, hypoxia-inducible factor; CDK5, cyclin-dependent kinase 5; ERs, estrogen receptors; PI3K, phosphatidylinositol 3-kinase; AKT, protein kinase B; NOTCH, locus notch homolog protein; BCL-2, B-cell lymphoma; Bax, BCL-2-associated X protein; MEK, mitogen-activated protein kinase; ROS, reactive oxygen species; RAS, rat sarcoma; RAF, rat accelerated fibrosarcoma.

Activation of the NRF2/ARE signaling pathway

Numerous pathways involved in cell proliferation, including factor kappa B (NF-κB), nuclear factor erythroid 2-related factor 2 (NRF2), and hypoxia-inducible factors (HIFs), are affected by oxidative stress (Hielscher and Gerecht, 2015; He et al., 2020). The NF-κB protein complex regulates DNA transcription and inflammatory production as well as cell survival, proliferation, and apoptosis (DiDonato et al., 2012). NF-κB is activated by the phosphatidylinositol 3-kinase (PI3K)/AKT (protein kinase B)/extracellular signal-regulated kinase (ERK) signaling pathways (He et al., 2021). Additionally, oxidative stress activates NRF2 through PI3K/AKT/ERK signaling (Brasil et al., 2021). NRF2 regulates the body’s defense system in response to oxidative stress. Specifically, this factor binds to the nucleus’s antioxidant response element (ARE) to initiate the transcription of cell-protective antioxidant genes (Tonelli et al., 2018).

Studies have shown that lutein inhibits oxidative stress and NF-κB by activating the NRF2/ARE signaling pathways (Wu et al., 2015; Frede et al., 2017). For example, a survey of breast cancer cells demonstrated that lutein hinders cell proliferation by suppressing the NF-κB signaling pathway and oxidative stress through the activation of the NRF2/ARE signaling pathways (Chang et al., 2018). Another study of breast cancer cells showed that lutein inhibited reactive oxygen species levels by activating NRF2 signaling and decreased the protein expression of AKT/ERK1/2 and NF-κB (Kavalappa et al., 2021) (Fig. 2).

Inhibition of the HIF-1α/Notch signaling pathway

HIFs (HIF-α and HIF-β) are heterodimeric transcription factors that play a role in the response of cells to hypoxia as well as in the activation of signaling pathways involved in cell survival, growth, invasion, angiogenesis, proliferation, and metastasis (Elzakra and Kim, 2021). Hypoxia activates the neurogenic locus notch homolog protein (Notch). Notch signaling is a critical cellular pathway that plays an essential role in cell growth, proliferation, differentiation, and apoptosis (Malekan et al., 2021). Studies have demonstrated that the HIF-1α/Notch signaling pathway is crucial for cancer progression (Malekan et al., 2021). According to various studies, lutein prevents the development of many diseases, including cancer, by inhibiting HIF (Li et al., 2012; Jia et al., 2017; Sharavana and Baskaran, 2017). A study of human breast cancer cell lines demonstrated that lutein inhibits the HIF-1α/Notch signaling pathway (Li et al., 2018) (Fig. 2).

Effect on the RAS-ERK and β-catenin signaling pathways

Some cellular processes, such as proliferation, differentiation, growth, and apoptosis, are regulated by the rat sarcoma (RAS)-ERK and β-catenin signaling pathways (Jeong et al., 2018). Studies have shown that mutagens in the β-catenin, RAS-ERK, and PI3K/AKT pathways play essential roles in tumorigenesis (Jeong et al., 2018; Ryu et al., 2021; Stefani et al., 2021). In this regard, it has been demonstrated that lutein decreased the protein expression of the Kirsten rat sarcoma virus, protein kinase B/AKT, and β-catenin pathways in rats with colon cancer (Reynoso-Camacho et al., 2011) (Fig. 2).

Effects on gene expression related to cell growth and proliferation

Lutein also affects the expression of essential genes related to cell growth and proliferation. Studies have found that these processes are regulated by insulin-like growth factor receptor (IGFR), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 6 (MAPK6), cyclin-dependent kinase 5 (CDK5), and glutathione S-transferase Pi 1 (GSTP1) (Gomes et al., 2012; Kryza et al., 2020; Zhang et al., 2020; Cai et al., 2021; Carter et al., 2021; Silva Rocha et al., 2021). A study of a prostate cancer cell line revealed that lutein inhibited the expression of the IGFR, EGFR, IGF2, MAPK6, PI3KCG, and CDK5 genes, but increased that of GSTP1 (Rafi et al., 2015).

In summary, lutein plays a significant role in cancer biology by regulating key signaling pathways and gene expression linked to tumorigenesis. Future research should investigate these mechanisms in order to develop potential cancer prevention and treatment strategies.

Apoptotic mechanisms

According to the findings of this review, lutein inhibits cancer progression by inducing apoptosis. This compound affects several apoptosis-related genes, increasing the activity of some and decreasing that of others. Apoptosis is regulated by proteins of the B-cell lymphoma (BCL-2) family, including anti-apoptotic (BCL-2, Bcl-xl, BCL-w, B-fl) and proapoptotic (BAX, BAK, BAD) proteins (Huang et al., 2019; Warren et al., 2019).

Lutein affects the expression of several essential genes involved in apoptosis. Caspases are members of the cysteine protease family that play an essential role in the initiation of apoptosis by increasing the expression of proapoptotic proteins (Van Opdenbosch and Lamkanfi, 2019). Studies have shown that the P53, Bax, and caspase-3 genes are tumor suppressors significantly involved in initiating apoptosis (Katifelis et al., 2018; Changizi et al., 2021). A study of human cervical carcinoma demonstrated that lutein induced apoptosis by activating Bax and caspase-3 (Gansukh et al., 2019). Similarly, another study of human lung cancer cells showed that lutein increased the expression of Bax and, conversely, reduced that of BCL-2 (Yamagata et al., 2017). Also, an investigation of human breast cancer cell lines revealed that lutein inhibited cell growth and induced apoptosis by decreasing BCL-2 expression and increasing Bax/P53 signaling (Gong et al., 2018) (Fig. 2). In summary, lutein plays a crucial role in inducing apoptosis by regulating the genes associated with this process. It increases the expression of pro-apoptotic proteins and tumor suppressors while reducing anti-apoptotic factors, which highlights its potential as an agent for cancer prevention and treatment. However, several of the studies examined did not show a protective effect of lutein against ERs (Rock et al., 1996; Bakker et al., 2016), DNA damage (Astley et al., 2002, 2004; Mousseau et al., 2005; Woelfelschneider et al., 2008), cell proliferation (Arunkumar et al., 2015), and cell growth (Arunkumar et al., 2015).

Bioavailability of lutein

Lutein is insoluble in aqueous environments in the human digestive tract because of its lipophilic properties (Ochoa Becerra et al., 2020). The bioavailability of lutein is mainly affected by food sources, fat contents, and the amount of dietary fiber (Eisenhauer et al., 2017), and supplementation can increase its absorption (DiSilvestro et al., 2015). The intestinal absorption of lutein from food is low, therefore nanoparticles and liposomes are commonly used to compensated for this shortcoming (Ochoa Becerra et al., 2020). According to Astley et al. (2004), liposomal lutein protects against DNA damage. Moreover, Arunkumar et al. (2015) reported that lutein nanocapsules had a more significant antiproliferative effect compared with micellar lutein. The lack of sufficient sample sizes, low consumption of food sources containing lutein, and low doses of lutein reported in the above-mentioned studies may have also contributed to the results not meeting expectations.

Strengths and limitations of the study

The strength of the present study consisted in the use of several reliable databases for the literature search, which increased the chances of including more articles and thus the accuracy of the systematic review. However, this review has several limitations, including the inability to conduct a meta-analysis due to the heterogeneity of the studies examined, the potential for publication bias, and the need to include additional RCT studies. Overall, animal and cellular studies have shown that lutein can induce apoptosis and inhibit cancer cell growth, invasion, proliferation, migration, adhesion, and metastasis. As a result, the risk of cancer can be reduced by treatment with lutein. The human studies examined have shown that the effects of lutein on cancer are minimal, highlighting the need for further clinical research in this area.

SUPPLEMENTARY MATERIALS

Supplementary materials can be found via https://doi.org/10.3746/pnf.2025.30.3.250

pnfs-30-3-250-supple.pdf (147.4KB, pdf)

ACKNOWLEDGEMENTS

This research is related to PhD student’s thesis of the first author.

Footnotes

FUNDING

This study was approved by The Deputy for Research and Technology at Tabriz University of Medical Sciences, Tabriz, Iran, under Grant No. 70144.

AUTHOR DISCLOSURE STATEMENT

The authors declare no conflict of interest.

AUTHOR CONTRIBUTIONS

Concept and design: SK and MA. Analysis and interpretation: SK and MA. Data collection: FB. Writing the article: FB. Critical revision of the article: SK and MA. Final approval of the article: all authors. Statistical analysis: FB. Obtained funding: SK and MA. Overall responsibility: SK and MA.

References

  1. Abdel-Aal ESM, Akhtar H, Zaheer K, Ali R. Dietary sources of lutein and zeaxanthin carotenoids and their role in eye health. Nutrients. 2013;5:1169–1185. doi: 10.3390/nu5041169. https://doi.org/10.3390/nu5041169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arunkumar R, Prashanth KVH, Manabe Y, Hirata T, Sugawara T, Dharmesh SM, et al. Biodegradable poly (lactic-co-glycolic acid)-polyethylene glycol nanocapsules: An efficient carrier for improved solubility, bioavailability, and anticancer property of lutein. J Pharm Sci. 2015;104:2085–2093. doi: 10.1002/jps.24436. https://doi.org/10.1002/jps.24436. [DOI] [PubMed] [Google Scholar]
  3. Astley SB, Elliott RM, Archer DB, Southon S. Increased cellular carotenoid levels reduce the persistence of DNA single-strand breaks after oxidative challenge. Nutr Cancer. 2002;43:202–213. doi: 10.1207/S15327914NC432_11. https://doi.org/10.1207/s15327914nc432_11. [DOI] [PubMed] [Google Scholar]
  4. Astley SB, Hughes DA, Wright AJ, Elliott RM, Southon S. DNA damage and susceptibility to oxidative damage in lymphocytes: effects of carotenoids in vitro and in vivo. Br J Nutr. 2004;91:53–61. doi: 10.1079/BJN20031028. https://doi.org/10.1079/bjn20031028. [DOI] [PubMed] [Google Scholar]
  5. Bakker MF, Peeters PH, Klaasen VM, Bueno-de-Mesquita HB, Jansen EH, Ros MM, et al. Plasma carotenoids, vitamin C, tocopherols, and retinol and the risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition cohort. Am J Clin Nutr. 2016;103:454–464. doi: 10.3945/ajcn.114.101659. https://doi.org/10.3945/ajcn.114.101659. [DOI] [PubMed] [Google Scholar]
  6. Behbahani M. Evaluation of in vitro anticancer activity of Ocimum basilicum, Alhagi maurorum, Calendula officinalis and their parasite Cuscuta campestris. PLoS One. 2014;9:e116049. doi: 10.1371/journal.pone.0116049. https://doi.org/10.1371/journal.pone.0116049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bitsie KR, Cheng TD, McCann SE, Zirpoli G, Yao S, Bandera EV, et al. Dietary vitamin A and breast cancer risk in black women: The African American Breast Cancer Epidemiology and Risk (AMBER) consortium. J Nutr. 2021;151:3725–3737. doi: 10.1093/jn/nxab278. https://doi.org/10.1093/jn/nxab278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Black HS, Boehm F, Edge R, Truscott TG. The benefits and risks of certain dietary carotenoids that exhibit both anti- and pro-oxidative mechanisms－A comprehensive review. Antioxidants. 2020;9:264. doi: 10.3390/antiox9030264. https://doi.org/10.3390/antiox9030264. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Brasil FB, Bertolini Gobbo RC, Souza de Almeida FJ, Luckachaki MD, Dall'Oglio EL, de Oliveira MR. The signaling pathway PI3K/Akt/Nrf2/HO-1 plays a role in the mitochondrial protection promoted by astaxanthin in the SH-SY5Y cells exposed to hydrogen peroxide. Neurochem Int. 2021;146:105024. doi: 10.1016/j.neuint.2021.105024. https://doi.org/10.1016/j.neuint.2021.105024. [DOI] [PubMed] [Google Scholar]
  10. Brewczyński A, Jabłońska B, Kentnowski M, Mrowiec S, Składowski K, Rutkowski T. The association between carotenoids and head and neck cancer risk. Nutrients. 2021;14:88. doi: 10.3390/nu14010088. https://doi.org/10.3390/nu14010088. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cai Q, Zhou W, Wang W, Dong B, Han D, Shen T, et al. MAPK6-AKT signaling promotes tumor growth and resistance to mTOR kinase blockade. Sci Adv. 2021;7:eabi6439. doi: 10.1126/sciadv.abi6439. https://doi.org/10.1126/sciadv.abi6439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Campestrini LH, Melo PS, Peres LEP, Calhelha RC, Ferreira I, Alencar SM. A new variety of purple tomato as a rich source of bioactive carotenoids and its potential health benefits. Heliyon. 2019;5:e02831. doi: 10.1016/j.heliyon.2019.e02831. https://doi.org/10.1016/j.heliyon.2019.e02831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Carter AM, Kumar N, Herring B, Tan C, Guenter R, Telange R, et al. Cdk5 drives formation of heterogeneous pancreatic neuroendocrine tumors. Oncogenesis. 2021;10:83. doi: 10.1038/s41389-021-00372-5. https://doi.org/10.1038/s41389-021-00372-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Castro-Puyana M, Pérez-Sánchez A, Valdés A, Ibrahim OHM, Suarez-Álvarez S, Ferragut JA, et al. Pressurized liquid extraction of Neochloris oleoabundans for the recovery of bioactive carotenoids with anti-proliferative activity against human colon cancer cells. Food Res Int. 2017;99:1048–1055. doi: 10.1016/j.foodres.2016.05.021. https://doi.org/10.1016/j.foodres.2016.05.021. [DOI] [PubMed] [Google Scholar]
  15. Cha KH, Koo SY, Lee DU. Antiproliferative effects of carotenoids extracted from Chlorella ellipsoidea and Chlorella vulgaris on human colon cancer cells. J Agric Food Chem. 2008;56:10521–10526. doi: 10.1021/jf802111x. https://doi.org/10.1021/jf802111x. [DOI] [PubMed] [Google Scholar]
  16. Chang CJ, Lin JF, Chang HH, Lee GA, Hung CF. Lutein protects against methotrexate-induced and reactive oxygen species-mediated apoptotic cell injury of IEC-6 cells. PLoS One. 2013;8:e72553. doi: 10.1371/journal.pone.0072553. https://doi.org/10.1371/journal.pone.0072553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Chang J, Zhang Y, Li Y, Lu K, Shen Y, Guo Y, et al. NrF2/ARE and NF-κB pathway regulation may be the mechanism for lutein inhibition of human breast cancer cell. Future Oncol. 2018;14:719–726. doi: 10.2217/fon-2017-0584. https://doi.org/10.2217/fon-2017-0584. [DOI] [PubMed] [Google Scholar]
  18. Changizi Z, Moslehi A, Rohani AH, Eidi A. Chlorogenic acid induces 4T1 breast cancer tumor's apoptosis via p53, Bax, Bcl-2, and caspase-3 signaling pathways in BALB/c mice. J Biochem Mol Toxicol. 2021;35:e22642. doi: 10.1002/jbt.22642. https://doi.org/10.1002/jbt.22642. [DOI] [PubMed] [Google Scholar]
  19. Chavda V, Chaurasia B, Garg K, Deora H, Umana GE, Palmisciano P, et al. Molecular mechanisms of oxidative stress in stroke and cancer. Brain Disord. 2022;5:100029. doi: 10.1016/j.dscb.2021.100029. https://doi.org/10.1016/j.dscb.2021.100029. [DOI] [Google Scholar]
  20. Chen HY, Yang CM, Chen JY, Yueh TC, Hu ML. Multicarotenoids at physiological levels inhibit metastasis in human hepatocarcinoma SK-Hep-1 cells. Nutr Cancer. 2015;67:676–686. doi: 10.1080/01635581.2015.1019633. https://doi.org/10.1080/01635581.2015.1019633. [DOI] [PubMed] [Google Scholar]
  21. Cheng HC, Chien H, Liao CH, Yang YY, Huang SY. Carotenoids suppress proliferating cell nuclear antigen and cyclin D1 expression in oral carcinogenic models. J Nutr Biochem. 2007;18:667–675. doi: 10.1016/j.jnutbio.2006.10.010. https://doi.org/10.1016/j.jnutbio.2006.10.010. [DOI] [PubMed] [Google Scholar]
  22. Demmig-Adams B, López-Pozo M, Stewart JJ, Adams WW., 3rd Zeaxanthin and lutein: photoprotectors, anti-inflammatories, and brain food. Molecules. 2020;25:3607. doi: 10.3390/molecules25163607. https://doi.org/10.3390/molecules25163607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. DiDonato JA, Mercurio F, Karin M. NF-κB and the link between inflammation and cancer. Immunol Rev. 2012;246:379–400. doi: 10.1111/j.1600-065X.2012.01099.x. https://doi.org/10.1111/j.1600-065X.2012.01099.x. [DOI] [PubMed] [Google Scholar]
  24. DiSilvestro RA, Thomas S, Harrison E, Epitropoulos A. A pilot comparison of phospolipidated lutein to conventional lutein for effects on plasma lutein concentrations in adult people. Nutr J. 2015;14:104. doi: 10.1186/s12937-015-0089-x. https://doi.org/10.1186/s12937-015-0089-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Eisenhauer B, Natoli S, Liew G, Flood VM. Lutein and zeaxanthin－food sources, bioavailability and dietary variety in age-related macular degeneration protection. Nutrients. 2017;9:120. doi: 10.3390/nu9020120. https://doi.org/10.3390/nu9020120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Elzakra N, Kim Y. HIF-1α metabolic pathways in human cancer. Adv Exp Med Biol. 2021;1280:243–260. doi: 10.1007/978-3-030-51652-9_17. https://doi.org/10.1007/978-3-030-51652-9_17. [DOI] [PubMed] [Google Scholar]
  27. Frede K, Ebert F, Kipp AP, Schwerdtle T, Baldermann S. Lutein activates the transcription factor Nrf2 in human retinal pigment epithelial cells. J Agric Food Chem. 2017;65:5944–5952. doi: 10.1021/acs.jafc.7b01929. https://doi.org/10.1021/acs.jafc.7b01929. [DOI] [PubMed] [Google Scholar]
  28. Gansukh E, Mya KK, Jung M, Keum YS, Kim DH, Saini RK. Lutein derived from marigold (Tagetes erecta) petals triggers ROS generation and activates Bax and caspase-3 mediated apoptosis of human cervical carcinoma (HeLa) cells. Food Chem Toxicol. 2019;127:11–18. doi: 10.1016/j.fct.2019.02.037. https://doi.org/10.1016/j.fct.2019.02.037. [DOI] [PubMed] [Google Scholar]
  29. Gao L, Gou N, Yao M, Amakye WK, Ren J. Food-derived natural compounds in the management of chronic diseases via Wnt signaling pathway. Crit Rev Food Sci Nutr. 2022;62:4769–4799. doi: 10.1080/10408398.2021.1879001. https://doi.org/10.1080/10408398.2021.1879001. [DOI] [PubMed] [Google Scholar]
  30. García-Gasca T, Fatell S, Villa-Treviño S, González de Mejía E. Effect of carotenoids against genotoxicity of diethylnitrosamine on rat hepatocytes. Toxicol In Vitro. 1998;12:691–698. doi: 10.1016/S0887-2333(98)00052-6. https://doi.org/10.1016/s0887-2333(98)00052-6. [DOI] [PubMed] [Google Scholar]
  31. Gaudet MM, Britton JA, Kabat GC, Steck-Scott S, Eng SM, Teitelbaum SL, et al. Fruits, vegetables, and micronutrients in relation to breast cancer modified by menopause and hormone receptor status. Cancer Epidemiol Biomarkers Prev. 2004;13:1485–1494. doi: 10.1158/1055-9965.1485.13.9. [DOI] [PubMed] [Google Scholar]
  32. Gomes IM, Maia CJ, Santos CR. STEAP proteins: from structure to applications in cancer therapy. Mol Cancer Res. 2012;10:573–587. doi: 10.1158/1541-7786.MCR-11-0281. https://doi.org/10.1158/1541-7786.Mcr-11-0281. [DOI] [PubMed] [Google Scholar]
  33. Gómez-García R, Campos DA, Oliveira A, Aguilar CN, Madureira AR, Pintado M. A chemical valorisation of melon peels towards functional food ingredients: Bioactives profile and antioxidant properties. Food Chem. 2021;335:127579. doi: 10.1016/j.foodchem.2020.127579. https://doi.org/10.1016/j.foodchem.2020.127579. [DOI] [PubMed] [Google Scholar]
  34. Gong X, Smith JR, Swanson HM, Rubin LP. Carotenoid lutein selectively inhibits breast cancer cell growth and potentiates the effect of chemotherapeutic agents through ROS-mediated mechanisms. Molecules. 2018;23:905. doi: 10.3390/molecules23040905. https://doi.org/10.3390/molecules23040905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Graff RE, Judson G, Ahearn TU, Fiorentino M, Loda M, Giovannucci EL, et al. Circulating antioxidant levels and risk of prostate cancer by TMPRSS2:ERG. Prostate. 2017;77:647–653. doi: 10.1002/pros.23312. https://doi.org/10.1002/pros.23312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Gross MD, Bishop TD, Belcher JD, Jacobs DR., Jr Induction of HL-60 cell differentiation by carotenoids. Nutr Cancer. 1997;27:169–173. doi: 10.1080/01635589709514520. [DOI] [PubMed] [Google Scholar]
  37. Gunasekera RS, Sewgobind K, Desai S, Dunn L, Black HS, McKeehan WL, et al. Lycopene and lutein inhibit proliferation in rat prostate carcinoma cells. Nutr Cancer. 2007;58:171–177. doi: 10.1080/01635580701328339. https://doi.org/10.1080/01635580701328339. [DOI] [PubMed] [Google Scholar]
  38. Haldosén LA, Zhao C, Dahlman-Wright K. Estrogen receptor beta in breast cancer. Mol Cell Endocrinol. 2014;382:665–672. doi: 10.1016/j.mce.2013.08.005. https://doi.org/10.1016/j.mce.2013.08.005. [DOI] [PubMed] [Google Scholar]
  39. He F, Antonucci L, Karin M. NRF2 as a regulator of cell metabolism and inflammation in cancer. Carcinogenesis. 2020;41:405–416. doi: 10.1093/carcin/bgaa039. https://doi.org/10.1093/carcin/bgaa039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. He Y, Sun MM, Zhang GG, Yang J, Chen KS, Xu WW, et al. Targeting PI3K/Akt signal transduction for cancer therapy. Signal Transduct Target Ther. 2021;6:425. doi: 10.1038/s41392-021-00828-5. https://doi.org/10.1038/s41392-021-00828-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Hielscher A, Gerecht S. Hypoxia and free radicals: Role in tumor progression and the use of engineering-based platforms to address these relationships. Free Radic Biol Med. 2015;79:281–291. doi: 10.1016/j.freeradbiomed.2014.09.015. https://doi.org/10.1016/j.freeradbiomed.2014.09.015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Huang K, O'Neill KL, Li J, Zhou W, Han N, Pang X, et al. BH3-only proteins target BCL-xL/MCL-1, not BAX/BAK, to initiate apoptosis. Cell Res. 2019;29:942–952. doi: 10.1038/s41422-019-0231-y. https://doi.org/10.1038/s41422-019-0231-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Iqbal MJ, Kabeer A, Abbas Z, Siddiqui HA, Calina D, Sharifi-Rad J, et al. Interplay of oxidative stress, cellular communication and signaling pathways in cancer. Cell Commun Signal. 2024;22:7. doi: 10.1186/s12964-023-01398-5. https://doi.org/10.1186/s12964-023-01398-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Jeong WJ, Ro EJ, Choi KY. Interaction between Wnt/β-catenin and RAS-ERK pathways and an anti-cancer strategy via degradations of β-catenin and RAS by targeting the Wnt/β-catenin pathway. NPJ Precis Oncol. 2018;2:5. doi: 10.1038/s41698-018-0049-y. https://doi.org/10.1038/s41698-018-0049-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Jia YP, Sun L, Yu HS, Liang LP, Li W, Ding H, et al. The pharmacological effects of lutein and zeaxanthin on visual disorders and cognition diseases. Molecules. 2017;22:610. doi: 10.3390/molecules22040610. https://doi.org/10.3390/molecules22040610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Jomova K, Raptova R, Alomar SY, Alwasel SH, Nepovimova E, Kuca K, et al. Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging. Arch Toxicol. 2023;97:2499–2574. doi: 10.1007/s00204-023-03562-9. https://doi.org/10.1007/s00204-023-03562-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Katifelis H, Lyberopoulou A, Mukha I, Vityuk N, Grodzyuk G, Theodoropoulos GE, et al. Ag/Au bimetallic nanoparticles induce apoptosis in human cancer cell lines via P53, CASPASE-3 and BAX/BCL-2 pathways. Artif Cells Nanomed Biotechnol. 2018;46(sup3):S389–S398. doi: 10.1080/21691401.2018.1495645. https://doi.org/10.1080/21691401.2018.1495645. [DOI] [PubMed] [Google Scholar]
  48. Kavalappa YP, Gopal SS, Ponesakki G. Lutein inhibits breast cancer cell growth by suppressing antioxidant and cell survival signals and induces apoptosis. J Cell Physiol. 2021;236:1798–1809. doi: 10.1002/jcp.29961. https://doi.org/10.1002/jcp.29961. [DOI] [PubMed] [Google Scholar]
  49. Kawahara T, Iwamoto T, Takashima I, Hanazawa R, Uemura K, Uemura Y, et al. Association of change in health-related quality of life and treatment discontinuation in metastatic breast cancer: a post hoc, exploratory analysis of two randomized clinical trials. Support Care Cancer. 2022;30:8367–8375. doi: 10.1007/s00520-022-07283-0. https://doi.org/10.1007/s00520-022-07283-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Kim JM, Araki S, Kim DJ, Park CB, Takasuka N, Baba-Toriyama H, et al. Chemopreventive effects of carotenoids and curcumins on mouse colon carcinogenesis after 1,2-dimethylhydrazine initiation. Carcinogenesis. 1998;19:81–85. doi: 10.1093/carcin/19.1.81. https://doi.org/10.1093/carcin/19.1.81. [DOI] [PubMed] [Google Scholar]
  51. Kryza T, Bock N, Lovell S, Rockstroh A, Lehman ML, Lesner A, et al. The molecular function of kallikrein-related peptidase 14 demonstrates a key modulatory role in advanced prostate cancer. Mol Oncol. 2020;14:105–128. doi: 10.1002/1878-0261.12587. https://doi.org/10.1002/1878-0261.12587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Lee KH. Pre- and co-treatment with xanthophyll enhances the anti-leukemic activity of adriamycin. J Photochem Photobiol B. 2008;92:175–179. doi: 10.1016/j.jphotobiol.2008.06.008. https://doi.org/10.1016/j.jphotobiol.2008.06.008. [DOI] [PubMed] [Google Scholar]
  53. Li SY, Fung FK, Fu ZJ, Wong D, Chan HH, Lo AC. Anti-inflammatory effects of lutein in retinal ischemic/hypoxic injury: in vivo and in vitro studies. Invest Ophthalmol Vis Sci. 2012;53:5976–5984. doi: 10.1167/iovs.12-10007. https://doi.org/10.1167/iovs.12-10007. [DOI] [PubMed] [Google Scholar]
  54. Li Y, Zhang Y, Liu X, Wang M, Wang P, Yang J, et al. Lutein inhibits proliferation, invasion and migration of hypoxic breast cancer cells via downregulation of HES1. Int J Oncol. 2018;52:2119–2129. doi: 10.3892/ijo.2018.4332. https://doi.org/10.3892/ijo.2018.4332. [DOI] [PubMed] [Google Scholar]
  55. Lu QY, Arteaga JR, Zhang Q, Huerta S, Go VL, Heber D. Inhibition of prostate cancer cell growth by an avocado extract: role of lipid-soluble bioactive substances. J Nutr Biochem. 2005;16:23–30. doi: 10.1016/j.jnutbio.2004.08.003. https://doi.org/10.1016/j.jnutbio.2004.08.003. [DOI] [PubMed] [Google Scholar]
  56. Malekan M, Ebrahimzadeh MA, Sheida F. The role of hypoxia-inducible factor-1alpha and its signaling in melanoma. Biomed Pharmacother. 2021;141:111873. doi: 10.1016/j.biopha.2021.111873. https://doi.org/10.1016/j.biopha.2021.111873. [DOI] [PubMed] [Google Scholar]
  57. Milani A, Basirnejad M, Shahbazi S, Bolhassani A. Carotenoids: biochemistry, pharmacology and treatment. Br J Pharmacol. 2017;174:1290–1324. doi: 10.1111/bph.13625. https://doi.org/10.1111/bph.13625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Min KB, Min JY. Serum carotenoid levels and risk of lung cancer death in US adults. Cancer Sci. 2014;105:736–743. doi: 10.1111/cas.12405. https://doi.org/10.1111/cas.12405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Mitra S, Rauf A, Tareq AM, Jahan S, Emran TB, Shahriar TG, et al. Potential health benefits of carotenoid lutein: An updated review. Food Chem Toxicol. 2021;154:112328. doi: 10.1016/j.fct.2021.112328. https://doi.org/10.1016/j.fct.2021.112328. [DOI] [PubMed] [Google Scholar]
  60. Molnár J, Gyémánt N, Mucsi I, Molnár A, Szabó M, Körtvélyesi T, et al. Modulation of multidrug resistance and apoptosis of cancer cells by selected carotenoids. In Vivo. 2004;18:237–244. [PubMed] [Google Scholar]
  61. Moreno FS, Toledo LP, de Conti A, Heidor R, Jordão A, Jr, Vannucchi H, et al. Lutein presents suppressing but not blocking chemopreventive activity during diethylnitrosamine-induced hepatocarcinogenesis and this involves inhibition of DNA damage. Chem Biol Interact. 2007;168:221–228. doi: 10.1016/j.cbi.2007.04.011. https://doi.org/10.1016/j.cbi.2007.04.011. [DOI] [PubMed] [Google Scholar]
  62. Mousseau M, Faure H, Hininger I, Bayet-Robert M, Favier A. Leukocyte 8-oxo-7,8-dihydro-2'-deoxyguanosine and comet assay in epirubicin-treated patients. Free Radic Res. 2005;39:837–843. doi: 10.1080/10715760500042860. https://doi.org/10.1080/10715760500042860. [DOI] [PubMed] [Google Scholar]
  63. Müller K, Carpenter KL, Challis IR, Skepper JN, Arends MJ. Carotenoids induce apoptosis in the T-lymphoblast cell line Jurkat E6. Free Radic Res. 2002;36:791–802. doi: 10.1080/10715760290032539. https://doi.org/10.1080/10715760290032539. [DOI] [PubMed] [Google Scholar]
  64. Murillo AG, DiMarco DM, Fernandez ML. The potential of non-provitamin A carotenoids for the prevention and treatment of non-alcoholic fatty liver disease. Biology. 2016;5:42. doi: 10.3390/biology5040042. https://doi.org/10.3390/biology5040042. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Neophytou CM, Panagi M, Stylianopoulos T, Papageorgis P. The role of tumor microenvironment in cancer metastasis: molecular mechanisms and therapeutic opportunities. Cancers (Basel) 2021;13:2053. doi: 10.3390/cancers13092053. https://doi.org/10.3390/cancers13092053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Ochoa Becerra M, Mojica Contreras L, Hsieh Lo M, Mateos Díaz J, Castillo Herrera G. Lutein as a functional food ingredient: Stability and bioavailability. J Funct Foods. 2020;66:103771. doi: 10.1016/j.jff.2019.103771. https://doi.org/10.1016/j.jff.2019.103771. [DOI] [Google Scholar]
  67. Omar WM, Ahmed AE, Raslan M, El-Nesr K, Ali MM, De Abdelmaksoud M, et al. Effect of lutein-rich extract on human cancer cells. Middle East J Cancer. 2021;12:147–150. doi: 10.30476/mejc.2020.82181.1063. https://doi.org/10.30476/mejc.2020.82181.1063. [DOI] [Google Scholar]
  68. Rafi MM, Kanakasabai S, Gokarn SV, Krueger EG, Bright JJ. Dietary lutein modulates growth and survival genes in prostate cancer cells. J Med Food. 2015;18:173–181. doi: 10.1089/jmf.2014.0003. https://doi.org/10.1089/jmf.2014.0003. [DOI] [PubMed] [Google Scholar]
  69. Reynoso-Camacho R, González-Jasso E, Ferriz-Martínez R, Villalón-Corona B, Loarca-Piña GF, Salgado LM, et al. Dietary supplementation of lutein reduces colon carcinogenesis in DMH-treated rats by modulating K-ras, PKB, and β-catenin proteins. Nutr Cancer. 2011;63:39–45. doi: 10.1080/01635581.2010.516477. https://doi.org/10.1080/01635581.2010.516477. [DOI] [PubMed] [Google Scholar]
  70. Rock CL, Saxe GA, Ruffin MT, August DA, Schottenfeld D. Carotenoids, vitamin A, and estrogen receptor status in breast cancer. Nutr Cancer. 1996;25:281–296. doi: 10.1080/01635589609514452. https://doi.org/10.1080/01635589609514452. [DOI] [PubMed] [Google Scholar]
  71. Ryu WJ, Han G, Lee SH, Choi KY. Suppression of Wnt/β-catenin and RAS/ERK pathways provides a therapeutic strategy for gemcitabine-resistant pancreatic cancer. Biochem Biophys Res Commun. 2021;549:40–46. doi: 10.1016/j.bbrc.2021.02.076. https://doi.org/10.1016/j.bbrc.2021.02.076. [DOI] [PubMed] [Google Scholar]
  72. Serpeloni JM, Barcelos GR, Friedmann Angeli JP, Mercadante AZ, Lourdes Pires Bianchi M, Antunes LM. Dietary carotenoid lutein protects against DNA damage and alterations of the redox status induced by cisplatin in human derived HepG2 cells. Toxicol In Vitro. 2012;26:288–294. doi: 10.1016/j.tiv.2011.11.011. https://doi.org/10.1016/j.tiv.2011.11.011. [DOI] [PubMed] [Google Scholar]
  73. Sharavana G, Baskaran V. Lutein downregulates retinal vascular endothelial growth factor possibly via hypoxia inducible factor 1 alpha and X-box binding protein 1 expression in streptozotocin induced diabetic rats. J Funct Foods. 2017;31:97–103. doi: 10.1016/j.jff.2017.01.023. https://doi.org/10.1016/j.jff.2017.01.023. [DOI] [Google Scholar]
  74. Shi X, Wang X, Yao W, Shi D, Shao X, Lu Z, et al. Mechanism insights and therapeutic intervention of tumor metastasis: latest developments and perspectives. Signal Transduct Target Ther. 2024;9:192. doi: 10.1038/s41392-024-01885-2. https://doi.org/10.1038/s41392-024-01885-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Silva Rocha F, da Silva Maués JH, Brito Lins Pereira CM, Moreira-Nunes CA, Rodriguez Burbano RM. Analysis of increased EGFR and IGF-1R signaling and its correlation with socio-epidemiological features and biological profile in breast cancer patients: A study in Northern Brazil. Breast Cancer. 2021;13:325–339. doi: 10.2147/BCTT.S308554. https://doi.org/10.2147/bctt.S308554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Sindhu ER, Kuttan R. Carotenoid lutein protects the kidney against cisplatin-induced acute renal failure. J Environ Pathol Toxicol Oncol. 2013;32:21–28. doi: 10.1615/JEnvironPatholToxicolOncol.2013004933. https://doi.org/10.1615/jenvironpatholtoxicoloncol.2013004933. [DOI] [PubMed] [Google Scholar]
  77. Sowmya PR, Arathi BP, Vijay K, Baskaran V, Lakshminarayana R. Role of different vehicles in carotenoids delivery and their influence on cell viability, cell cycle progression, and induction of apoptosis in HeLa cells. Mol Cell Biochem. 2015;406:245–253. doi: 10.1007/s11010-015-2442-y. https://doi.org/10.1007/s11010-015-2442-y. [DOI] [PubMed] [Google Scholar]
  78. Stefani C, Miricescu D, Stanescu-Spinu II, Nica RI, Greabu M, Totan AR, et al. Growth factors, PI3K/AKT/mTOR and MAPK signaling pathways in colorectal cancer pathogenesis: Where are we now? Int J Mol Sci. 2021;22:10260. doi: 10.3390/ijms221910260. https://doi.org/10.3390/ijms221910260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Sumantran VN, Zhang R, Lee DS, Wicha MS. Differential regulation of apoptosis in normal versus transformed mammary epithelium by lutein and retinoic acid. Cancer Epidemiol Biomarkers Prev. 2000;9:257–263. [PubMed] [Google Scholar]
  80. Sun Z, Yao H. The influence of di-acetylation of the hydroxyl groups on the anti-tumor-proliferation activity of lutein and zeaxanthin. Asia Pac J Clin Nutr. 2007;16 Suppl 1:447–452. [PubMed] [Google Scholar]
  81. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–249. doi: 10.3322/caac.21660. https://doi.org/10.3322/caac.21660. [DOI] [PubMed] [Google Scholar]
  82. Toledo LP, Ong TP, Pinho AL, Jordão A, Jr, Vanucchi H, Moreno FS. Inhibitory effects of lutein and lycopene on placental glutathione S-transferase-positive preneoplastic lesions and DNA strand breakage induced in Wistar rats by the resistant hepatocyte model of hepatocarcinogenesis. Nutr Cancer. 2003;47:62–69. doi: 10.1207/s15327914nc4701_8. https://doi.org/10.1207/s15327914nc4701_8. [DOI] [PubMed] [Google Scholar]
  83. Tonelli C, Chio IIC, Tuveson DA. Transcriptional regulation by Nrf2. Antioxid Redox Signal. 2018;29:1727–1745. doi: 10.1089/ars.2017.7342. https://doi.org/10.1089/ars.2017.7342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  84. Tsai YC, Wu WB, Chen BH. Preparation of carotenoids and chlorophylls from Gynostemma pentaphyllum (Thunb.) Makino and their antiproliferation effect on hepatoma cell. J Med Food. 2010;13:1431–1442. doi: 10.1089/jmf.2010.1165. https://doi.org/10.1089/jmf.2010.1165. [DOI] [PubMed] [Google Scholar]
  85. Ugocsai K, Varga A, Molnár P, Antus S, Molnár J. Effects of selected flavonoids and carotenoids on drug accumulation and apoptosis induction in multidrug-resistant colon cancer cells expressing MDR1/LRP. In Vivo. 2005;19:433–438. [PubMed] [Google Scholar]
  86. Van Hoang D, Pham NM, Lee AH, Tran DN, Binns CW. Dietary carotenoid intakes and prostate cancer risk: A case-control study from Vietnam. Nutrients. 2018;10:70. doi: 10.3390/nu10010070. https://doi.org/10.3390/nu10010070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  87. Van Opdenbosch N, Lamkanfi M. Caspases in cell death, inflammation, and disease. Immunity. 2019;50:1352–1364. doi: 10.1016/j.immuni.2019.05.020. https://doi.org/10.1016/j.immuni.2019.05.020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  88. Vijay K, Sowmya PRR, Arathi BP, Lakshminarayana R. Evaluation of anti-inflammatory and anti-proliferative effect of hydroxy-, keto-, and epoxy-carotenoids in RAW 264.7 and HL-60 cells. J Food Chem Nanotechnol. 2016;2:153–161. doi: 10.17756/jfcn.2016-024. https://doi.org/10.17756/jfcn.2016-024. [DOI] [Google Scholar]
  89. Vijay K, Sowmya PR, Arathi BP, Shilpa S, Shwetha HJ, Raju M, et al. Low-dose doxorubicin with carotenoids selectively alters redox status and upregulates oxidative stress-mediated apoptosis in breast cancer cells. Food Chem Toxicol. 2018;118:675–690. doi: 10.1016/j.fct.2018.06.027. https://doi.org/10.1016/j.fct.2018.06.027. [DOI] [PubMed] [Google Scholar]
  90. Warren CFA, Wong-Brown MW, Bowden NA. BCL-2 family isoforms in apoptosis and cancer. Cell Death Dis. 2019;10:177. doi: 10.1038/s41419-019-1407-6. https://doi.org/10.1038/s41419-019-1407-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  91. Woelfelschneider A, Popanda O, Lilla C, Linseisen J, Mayer C, Celebi O, et al. A distinct ERCC1 haplotype is associated with mRNA expression levels in prostate cancer patients. Carcinogenesis. 2008;29:1758–1764. doi: 10.1093/carcin/bgn067. https://doi.org/10.1093/carcin/bgn067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  92. Wu W, Li Y, Wu Y, Zhang Y, Wang Z, Liu X. Lutein suppresses inflammatory responses through Nrf2 activation and NF-κB inactivation in lipopolysaccharide-stimulated BV-2 microglia. Mol Nutr Food Res. 2015;59:1663–1673. doi: 10.1002/mnfr.201500109. https://doi.org/10.1002/mnfr.201500109. [DOI] [PubMed] [Google Scholar]
  93. Yamagata K, Fujiwara A, Onodera D, Motoki T. Lutein regulates the expression of apoptosis-related genes and stem cell markers in A549 human lung cancer cells. Nat Prod Commun. 2017;12:1934578X1701200616. doi: 10.1177/1934578X1701200616. https://doi.org/10.1177/1934578X1701200616. [DOI] [Google Scholar]
  94. Zaini RG, Brandt K, Clench MR, Le Maitre CL. Effects of bioactive compounds from carrots (Daucus carota L.), polyacetylenes, beta-carotene and lutein on human lymphoid leukaemia cells. Anticancer Agents Med Chem. 2012;12:640–652. doi: 10.2174/187152012800617704. https://doi.org/10.2174/187152012800617704. [DOI] [PubMed] [Google Scholar]
  95. Zhang L, Meng X, Pan C, Qu F, Gan W, Xiang Z, et al. piR-31470 epigenetically suppresses the expression of glutathione S-transferase pi 1 in prostate cancer via DNA methylation. Cell Signal. 2020;67:109501. doi: 10.1016/j.cellsig.2019.109501. https://doi.org/10.1016/j.cellsig.2019.109501. [DOI] [PubMed] [Google Scholar]
  96. Zhang WL, Zhao YN, Shi ZZ, Cong D, Bai YS. Lutein inhibits cell growth and activates apoptosis via the PI3K/AKT/mTOR signaling pathway in A549 human non-small-cell lung cancer cells. J Environ Pathol Toxicol Oncol. 2018;37:341–350. doi: 10.1615/JEnvironPatholToxicolOncol.2018027418. https://doi.org/10.1615/JEnvironPatholToxicolOncol.2018027418. [DOI] [PubMed] [Google Scholar]
  97. Zhang X, Yu S, Li X, Wen X, Liu S, Zu R, et al. Research progress on the interaction between oxidative stress and platelets: Another avenue for cancer? Pharmacol Res. 2023;191:106777. doi: 10.1016/j.phrs.2023.106777. https://doi.org/10.1016/j.phrs.2023.106777. [DOI] [PubMed] [Google Scholar]
  98. Zhang Y, Chang J, Jiang W, Ye X, Zhang S. Long non-coding RNA CASC9/microRNA-590-3p axis participates in lutein-mediated suppression of breast cancer cell proliferation. Oncol Lett. 2021;22:544. doi: 10.3892/ol.2021.12805. https://doi.org/10.3892/ol.2021.12805. [DOI] [PMC free article] [PubMed] [Google Scholar]

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