TABLE 1.
Anti-tumor action and mechanism of action of Naringin.
| Pharmacological action | Cell/Animal model | Mechanism of action |
|---|---|---|
| Blocking the tumorcell cycle and Inhibiting the tumorcell proliferation | Cervical Cancer C33A, HeLa (Lin et al., 2020), Stomach Cancer SNU-1 (Xu et al., 2021) | Inhibit PI3K/AKT, β-catenin/GSK-3β pathway; ↓c-Myc, Cyclin D1, CDK2, CDK4; ↑p21/cip1, p27/kip1; G0/G1 phase block |
| Prostate Cancer PCa (Erdogan et al., 2018) | Inhibit NF-kB pathway; ↓p50, ↑p21, p27, p53; G0/G1 phase block | |
| Triple-negative breast cancer MDAMB-231, BT-549 (Li et al., 2013) | Regulate the Wnt/β -catenin pathway; ↑p21, ↓p-Rb, Cyclin D1, Cyclin E; G0/G1 phase block | |
| Breast Cancer (El-Kersh et al., 2021) | Antiestrogenic and Inhibit-aromatase activity | |
| Colon and Rectal SW620 (Cheng et al., 2020a; Liqiong and Na, 2020) | Inhibit PI3K/AKT/mTOR pathway; ↓p-mTOR, CyclinD1, ↑ARHI, p21 | |
| Osteosarcoma MG63, U2OS (Ming et al., 2018) | ↓Zeb1, ↓Cyclin D1; G1 phase block | |
| Bladder Cancer 5637 (Kim et al., 2008) | Inhibit Ras/Raf/ERK pathway, ↑p21WAF1/cip1 ↓cyclin D1/E, CDK2, CDK4; G1 phase block | |
| Osteosarcoma MG63, U2OS (Yi et al., 2018) | ↓Zeb1, ↓Cyclin D1; G1 phase block | |
| Ovarian Cancer SKOV3/CDDP (Zhu et al., 2020) | Inhibit Wnt/catenin pathway; ↓β-catenin, c-Myc, cyclin D1 | |
| G1/S phase block | ||
| Cervical Cancer SiHA (Ramesh and Alshatwi, 2013) | G2/M phase block | |
| Colon and Rectal HCT116 (Cheng et al., 2020a), Stomach Cancer AGS (Raha et al., 2020) | Inhibit PI3K/AKT/mTOR pathway, ↓p-mTOR | |
| Triple-negative breast cancer (Raha et al., 2020) | Regulate Wnt/β-catenin pathway | |
| NSCLC Lung CancerA549, H460 (Zhongyuan et al., 2017) | Inhibit PI3K/AKT/mTOR pathway, ↓p-mTOR,↓p70S6K | |
| Melanoma A375 (Bing-yu et al., 2016) | Inhibit c-Src/AKT pathway; ↓PKM2, LDHA, HIF-1α; Inhibit aerobic glycolysis | |
| Glioblastoma U87 (Wei et al., 2020) | ↓CDK4/CDK6 | |
| Cervical Cancer ME-180 (Rui-ying et al., 2022) | ↑miR-628–5p | |
| Non-small cell lung cancer H69 (Chen et al., 2018) | Regulate NF-κB pathway, ↓VCAM-1, ↑ miR-126 | |
| Melanoma A875 (Guo et al., 2016) | Inhibit c-Src/AKT pathway; ↓CDK4/CDK6, ↓PKM2, LDHA, HIF-1α; Inhibit aerobic glycolysis | |
| Esophageal cancer Eca109 (Feng et al., 2021) | Inhibit the JAK/STAT pathway,↓p-STAT3/STAT3, ↓p-JAK2/JAK2 | |
| Inducing tumor cell apoptosis | Stomach Cancer AGS (Raha et al., 2020) | The mitochondrial pathway; ↓mTOR, Bcl-xL; ↑Bad |
| Cervical Cancer ME-180 (Rui-ying et al., 2022) | ↑miR-628–5p, Bax; ↓Bcl-2 | |
| Thyroid Cancer TPC-1, SW1736 (Zhou et al., 2019); glioma U87 (Wei et al., 2020), Stomach Cancer SUN-1 (Xu et al., 2021) | Inhibit PI3K/AKT pathway, ↑Caspase-3, cleaved Caspase-3, Bax; ↓survivin, Bcl-2 | |
| Melanoma A375, A875 (Guo et al., 2016) | Inhibit c-Src/AKT pathway, ↓Bcl2, ↑caspase-3, Bax | |
| Esophageal cancer Eca109 (Feng et al., 2021) | ↑BAX, CytC, caspase-3, -9, ↓Bcl2, Inhibit JAK/STAT pathway | |
| Cervical Cancer SiHa (Ramesh and Alshatwi, 2013), Liver Cancer HepG2 (Banjerdpongchai et al., 2016) | The mitochondrial pathway; ↑caspase-3, caspase-9, Bax, P53↓Bcl-xL; The death receptor pathway; ↑Fas, FADD, caspase-8 | |
| Cervical Cancer HeLa (Zeng et al., 2014) | ↓NF-κB p65, COX-2, caspase-1; ↑cleaved caspase-3 | |
| Colon Cancer HT29 (Albayrak et al., 2021), Thyroid Cancer B-CPAP (Li et al., 2022) | ROS-mediated ER stress; activate PERK/eIF2α/ATF4/CHOP pathway, ↑Bax, ↓Bcl-2 | |
| Cervical Cancer C33A (Lin et al., 2020) | Endoplasmic reticulum pathway; ↑CHOP, PARP1, caspase-3, activate eIF2α, ↑miR-628–5p, Bax, ↓Bcl-2 | |
| Ovarian Cancer SKOV3 (Zhu et al., 2020), Lung Cancer H1299 (Xuemei et al., 2018) | Inhibit PTEN/Akt pathway, ↓Bcl-2, Bcl-xL, survivin; ↑caspase-3, caspase-7 | |
| Colon Cancer SW620 (Liqiong and Na, 2020) | Regulate AKT pathway, ↓Bcl2, ↑caspase-3, Bax; ↑ARHI, Bax; ↓Bcl-2 | |
| Inhibit invasion and metastasis | Colon and Rectal HCT116, LOVO (Albayrak et al., 2021) | Inhibit miR-216a, ↓KIAA1199,↓CEMIP |
| Thyroid Cancer B-CPAP (Li et al., 2022) | Regulate PERK/eIF2α/ATF4/CHOP, ↑E-cadherin, ↓N-cadherin, Vimentin | |
| Melanoma A375 (Guo et al., 2016) | Inhibit c-Src/PI3K/AKT pathway, ↓MMP2, MMP9 | |
| Cervical Cancer ME-180 (Rui-ying et al., 2022) | Regulate miR-628–5p pathway, ↑E-cadherin, ↓N-cadherin, hinder EMT | |
| Prostate Cancer DU145, PC3 (Erdogan et al., 2018) | Inhibit NF-kB/ERK pathway, ↓Snail, Twist, hinder EMT | |
| Glioblastoma U251 (Aroui et al., 2016) | Inactivate p38 pathway, ↓MMP-2, MMP-9, ↑TIMP-1/2 | |
| Glioblastoma U87 (Aroui et al., 2020) | Inhibit ERK/P38/JNK pathway, ↓VEGFR2, ↓CD31, CD105mRNA, anti-angiogenic | |
| Induce autophagy of tumor cells | Stomach Cancer AGS (Raha et al., 2015) | Activate MAPK pathway, Inhibit PI3K/Akt/mTOR pathway, ↑Beclin-1, LC3B, MAPKs |
| Stomach Cancer SNU-1 (Xu et al., 2021) | Activate ERK/p38 pathway,↑Cathepsin D, ↑BH3-only Bad, ERK1/2, induce LMP mediated lysosomal cell death; Inhibit PI3K/AKT pathway, ↑LC3B, Beclin-1, ↓p62 | |
| Reverse tumor cell drug resistance and increase sensitization | Ovarian cancer SKOV3/CDDP (Zhu et al., 2020) | Inhibit NF-κB pathway, ↓P-gp, COX-2 ↓MDR1 mRNA, MRP2 mRNA, MRP2 |
| Prostate Cancer DU145, PC3, LNCaP (Erdogan et al., 2018) | Enhance the cytotoxic effects of paclitaxel | |
| Lung Cancer persister A549/DDP (Mei-ying et al., 2019) | ↑Bax, ↓P-gp, MRP1, p-Akt, CXCR4 | |
| Anti-inflammatory | C57BL/6 Male mousemodel (Zhang et al., 2016) | Inhibit NF-κB/IL-6/STAT3 pathway, ↓COX-2, MDSCs, GM-CSF/M-CSF, TNF-α; ↑ macrophage, CD4+T, And CD8 + T cell number |
| (ApcMin/+)Male mouse model (Zhang et al., 2018) | Inhibit GSK-3β/APC/β-catenin pathway, ↓Cox-2, TNF-α, PGE2; ↓IL-6 | |
| Reduce adverse reactions | Cervical Cancer HeLa (Liu et al., 2017) | Improve weight loss, reduce cardiotoxicity, hepatorenal toxicity ↓ALT、AST、ALP、TBIL; ↓IL-6、TNF-a; ↓MDA、NO; ↑ SOD、CAT、GPx、GR、GSH; ↓Cr、BUN |
| Liver tissue of Male albino rats (Elsawy et al., 2020) | ||
| Liver and kidney tissues of male adult Sprague-Dawley rats (Gelen et al., 2018) | ||
| Enhance and activate immunity | Human monocyte-derivedmacrophages, The C57BL/6 n mouse (Fujiwara et al., 2018) | Activate lymph node CD169 positive macrophages, ↑ CD169 |