Table 1.
Characteristics of the in vitro studies included in the systematic review on curcumin and breast cancer.
| Author/Year/Country | Type of Cell/Model | Intervention | Outcomes | Conflict of Interest | |||
|---|---|---|---|---|---|---|---|
| Antitumor Activity | |||||||
| Concentration (Component) | Treatment Duration | Cell Proliferation In Vitro | Cell Viability | Apoptosis and/or Cell Cycle Interruption | |||
| Abbaspour and Afshar, 2018 [27] Iran |
MCF-7 Human |
Curcumin at 10, 20 and 30 μg/mL |
24, 48, and 72 h | MTT assay ↓ cell proliferation owing to downregulation of ODC1 and ADA gene expression. |
MTT assay ↓ viability of cells in a time- and dose-dependent manner. |
Not reported | None |
| Abuelba et al., 2015 [28] Romania |
MDA-MB-231 Human |
Curcumin at 15–19 μM |
24, 48, and 72 h | MTT assay ↓ cell proliferation upon treatment with 15 μM curcumin. |
MTT assay ↓ cell viability by up to 25% upon treatment with 15 μM curcumin. |
MTT assay Pro-apoptotic effects on MDA-MB-231 cells cultured in a single layer, without photoactivation. |
None |
| Bimonte et al., 2015 [7] Italy |
MDA.MB231 Human |
Curcumin at 10 and 50 μM |
48 h | MTT assay Inhibition of breast cancer cell migration in 48 h. ↓ cell proliferation (p < 0.05). |
Not reported | Flow cytometry Curcumin (10 μM) ↑ apoptosis (p < 0.0001). |
None |
| Calaf et al., 2018 [31] Chile |
MCF7 MDA-MB-231 Human |
Curcumin at 30 µM |
48 h | Not reported | Not reported | Flow cytometry Apoptosis MDA-MB-231: 14.2% MCF7: 4.6% |
None |
| Chiu and Su, 2009 [33] China |
MDA-MB-231 Human |
Curcumin at 10, 20, and 30 μg/mL |
48 h | MTT Assay ↓ proliferation of MDA-MB-231 cells via p21 expression. |
Not reported | Flow cytometry Curcumin induced apoptosis via positive regulation of the Bax:Bcl-2 ratio. |
None |
| Choudhuri et al., 2002 [34] India |
MCF-7 Human |
Curcumin at 10 and 25 μM |
24 h | Quantitative image analysis Cessation of cell growth followed by significant cell death. Optimal inhibition was obtained upon treatment with 25 μM curcumin. |
Not reported | Quantitative image analysis techniques Curcumin induced apoptosis. |
None |
| Coker-Gurkan et al., 2019 [35] Turkey |
T47D Human |
Curcumin at 30 µM | 24 and 48 h | Not reported | MTT assay ↓ cell viability by 48% and 60% upon treatment with 20 µM curcumin (p < 0.0024). |
Double staining with Annexin-V/PI Curcumin induced apoptosis in 10.9% and 5.2% of the cell populations. |
None |
| Coker-Gurkan et al., 2018 [36] Turkey |
MCF-7 MDA-MB-231 Human |
Curcumin at 30 µM | 24 and 48 h | Not reported | MTT assay ↓ cell viability MCF-7 cells by 49% and of MDA-MB-453 cells by 48% upon treatment for 24 h with 20 µM curcumin |
MTT assay Curcumin induced apoptotic cell death. |
None |
| Fan et al., 2016 [37] China |
MDA-MB-231 Human |
Curcumin at 50 μg/mL | 24 h | Not reported | MTT assay ↓ cell viability (% NR) (P:NR) |
MTT assay Curcumin induced apoptosis. |
None |
| Ghosh et al., 2021 [39] India |
MDA-MB 231 Human |
Curcumin at 50 μg/mL Nanostructured platform Nanoparticles, MSN-Curcumin (MSN-C), and MSN-Hyaluronic acid-Curcumin (MSN-HA-C) |
48 h | MTT Assay MSN-HA-C blocked cell proliferation, in contrast to free curcumin. The treatment agent exhibited anticancer properties at 20 μg/mL. |
Not reported | MTT assay Cell death MSN-HA-C: 58% MSN-C: 34% (with equivalent dose of 12 μg/mL curcumin). MDA-MB-231 cycle arrest ↓ G1-phase cells: 32.5% Control: 54.6% G2/M phase cells: 37.8% Controls: 11.4%. |
None |
| Hashemzehi et al., 2018 [42] Iran |
MCF-7 Human |
Curcumin at 1 mM Nanostructured platform Nano-curcumin—phytosomalcurcumin |
24 h | Transwell assay ↓ cell invasion MTT assay ↓ cell growth in a dose-dependent manner. |
Not reported | Not reported | None |
| He et al., 2019 [43] China |
4T1 Mouse |
Curcumin at 50 μg/mL Nanostructured platform Polymeric micellar NPs [amphiphilic diblock copolymer—mPEG-b-PLG (Se) -TP] |
48 h | Not reported | MTT assay ↓ of cell viability upon treatment with CUR-NP and Free CUR: 15% |
Not reported | None |
| Hu et al., 2018 [44] China |
T47D, MCF7 Human |
Curcumin at 10 or 30 µM |
72 h | MTT assay ↓ cell proliferation |
Not reported | Flow cytometry Apoptosis T47D cells: 13.87% and 30.09%. MCF7 cells: 15.14% and 35.04%. |
None |
| Hua et al., 2010 [45] China |
MDA-MB-435 Human |
Curcumin at 10, 25, 50, and 75 μM | 12, 24, or 48 h. | MTT assay ↓ cell proliferation, inducing arrest in the G1 phase. |
Not reported | Not reported | NR |
| Ji et al., 2020 [47] China |
MDA-MB-231 Human |
Curcumin at 50 μg/mL |
24 h | Not reported | Not reported | Flow cytometry Apoptosis HA@CUR-NCs 80%. |
None |
| Jiang et al., 2013 [48] China |
MCF-7/LCC2 and LCC9 Human |
Curcumin at 10 and 30 μM |
24, 48, 72, and 96 h | Colony formation assay ↓ colony formation Complete suppression of colony formation upon treatment with 30 μM curcumin. |
Not reported | Annexin-V/PI staining and flow cytometry 30 μM curcumin caused a significant increase (28.72% in MCF-7 cells, 31.36% in MCF-7/LCC2 cells, and 34.70% in MCF-7/LCC9 cells) in the percentage of late apoptotic cells. |
None |
| Jin et al., 2017 [49] China and USA |
MCF-7 Human |
Curcumin at 10 µg/mL Nanostructured platform CUR-NP; GE11-CUR-NP; Free CUR |
24 h | Not reported | Nanostructured platform CUR-NP, GE11-CUR-NP, and Free CUR |
Flow cytometry Apoptosis CUR-NP: 14.9%; GE11-CUR-NP: 18.9%; Free CUR 11.0%. |
None |
| Jung et al., 2018 [50] South Korea |
MDA-MB-468 Human |
Curcumin at 5 and 10 μM |
72 and 96 h | Colony formation assay ↓ number of colonies over 2 weeks to 36.9 ± 7.7% upon treatment with 5 µM curcumin. |
Unclear method ↓ significantly decreased cell viability (41.5 ± 2.8% of basal level) upon treatment with 10 µM curcumin |
Not reported | None |
| Kim et al., 2012 [51] Coreia do Sul |
MCF-7 Human |
Curcumin at 1, 5, 10, 30, and 50 μM |
24 h | Not reported | MTT assay Curcumin exerted no effect on the viability of MCF-7 cells |
Not reported | None |
| Kumari et al., 2017 [52] India |
MDA-MB-231 Human |
Curcumin at 50 and 100 μg/mL Nanostructured platform free CUR and CUR-mPEG-PLA-Ch micelles |
24 h | Not reported | MTT assay CUR: 55.26 ± 3.7% Free CUR: 66.84 ± 2.4% (p = 0.079) |
Not reported | None |
| Kumari et al., 2020 [53] India |
MDA-MB-231 Human 4T1 Mouse |
Curcumin at 50 μg/mL Nanostructured platform CUR treatment (Free CUR group—24 μg/mL) and CUR-HSA-DOPE NPs treatment (CUR-HSA-DOPE group) |
6 and 24 h | Not reported | MTT Assay MDA-MB-231 Cur-HSA-DOPE NPs 24.34 ± 6.1% and 33.99 ± 4.5% free CUR 34.87 ± 4.9% and 43.12 ± 2.4% 50 μg/mL curcumin 4T1 CUR-HSA-DOPE NPs 25.2 ± 5.8% and 11.9 ± 8.6% free CUR 34.5 ± 6.6% and 48.3 ± 7.2% 50 μg of curcumin |
Immunofluorescence TUNEL assay ↑ Apotosis CUR-HSA-DOPE NPs |
None |
| Kumari et al., 2016 [54] India |
MDA-MB-231 Human |
Curcumin at 50 μg/mL Curcumin and curcumin-loaded nanoparticles (curcumin in mPEG-PLA micelles) (CUR-HSA-DOPE NPs) |
24 h | Not reported | MTT Assay CUR-mPEG-PLA231 35.1 ± 8.5 free CUR 65.7 ± 1.0% 50 μg/mL |
Not reported | None |
| Laha et al., 2018 [55] India and USA |
MDA-MB-468 Human |
Curcumin at 20, 40, 60, 80, 100, and 120 mM |
12 and 24 h | Not reported | Not reported | Annexin V-FITC staining Apoptotic cells: 25% and 91%. |
None |
| Lai et al., 2012 [56] China |
MCF-7, BT-474, MDA-MB-231, and normal breast cells Human |
Curcumin at 10 μg/mL |
72 h | Colorimetric analysis of sulforhodamine B ↓ cell proliferation (MCF-7, BT-474, and MDA-MB-231 cells). |
Not reported | Not reported | None |
| Li et al., 2018 [3] China |
MDA-MB-231 Human |
Curcumin at 10 g/mL Nanostructured platform curcumin and curcumin nanoparticle MSN/IR780-PEI-FA 160 mg/kg |
24 and 48 h | Not reported | Not reported | Flow cytometry CUR and free MSN/CUR induced the G2/M phase of the cell cycle. |
|
| Liu et al., 2013 [58] China |
4T1 Mouse |
Curcumin at 100 μg/mL Nanostructured platform Nanoparticle with self-assembled polymeric micelles (CUR-M) loaded with curcumin (CUR) |
48 h | Not reported | MTT assay Both CUR-M and Free CUR drastically inhibited cell growth in a dose-dependent manner. |
TUNEL assay by immunofluorescence staining Apoptotic index CUR-M: 15.77 ± 2.74%, Free CUR: 9.42 ± 2.13% p < 0.001) |
None |
| Liu et al., 2009 [58] China |
MDA-MB-231 Human |
Curcumin at 1, 1.25, 2.5, 5, 10, and 20 mg/mL |
24 and 48 h | Method (NR) Inhibition of cell growth by 60–70% with 1.25 mg/mL curcumin. Inhibition of cell growth by 50–60% with 2.5 mg/mL curcumin. |
Not reported | Not reported | NR |
| Lv et al., 2014 [61] China |
MDA-MB-231 Human |
Curcumin at 1–100 μL |
24 and 48 h | Not reported | MTT assay ↓ significant reduction in the number of viable cells in a time- and dose-dependent manner. |
Flow cytometry of fixed nuclei ↑ in the number of apoptotic cells in a dose-dependent manner. |
None |
| Masuelli et al., 2013 [63] Italy |
MDA-MB-231, MDA -MB-435, MDA-MB-453, MDA-MB-468, T-47D, MCF7, BT-474, SK-BR-3 Human Mammary cancer cells (H-2”) (TUBO) Humanized mouse Mammary cancer cells (H-2”) (TUBO) Mouse |
Curcumin 6 to 50 pM |
24 and 48 h | Not reported | Not reported | Pro-apoptotic Bax and anti-apoptotic Bcl-2 expression CUR induced apoptosis in all investigated cell types. |
None |
| Mehta et al., 1997 [64] USA |
MCF7 Human |
Curcumin 1 to 3 μg/mL |
72 h | [3H]thymidine incorporation and flow cytometry. Cell growth inhibition in a time- and dose-dependent manner, correlated with the inhibition of ornithine decarboxylase activity. |
Not reported | Flow cytometry Curcumin-induced cell death was not due to apoptosis or any significant change in the expression of apoptosis-related genes, including the Bcl-2, p53, cyclin B, and transglutaminase genes. |
NR |
| Montazeri et al., 2017 [65] Iran |
MCF7 Human |
Curcumin at 23, 17, and 14 µM Dendrosomal curcumin (DNC) for 48 h (28–35 μM) and 72 h (23–25 μM) |
24, 48, and 72 h | Not reported | Not reported | Flow cytometry Total apoptosis by DNC: 24 h: 30.34 ± 0.011% 48 h: 33.83 ± 0.005% 72 h: 61.83 ± 0.009% |
None |
| Mukhopadhyay et al., 2020 [67] India |
MDA-MB-231 Human |
5 mg of curcumin Nanostructured platform Polymeric NPs PLGA/PVA with or without folate (F) |
24 h | Not reported | Not reported | Flow cytometry Apoptosis CUR-NP-F: 29% Free CUR: 20% |
|
| Sarighieh et al., 2020 [70] Irã |
MCF7 Human |
Curcumin 5, 10, 20, 40, 80, and 160 μM |
24 h | Not reported | MTT assay Curcumin decreased the cell viability of MCF-7 cells. |
Flow cytometry Apoptosis 24.6% |
None |
| Sun Shih-Han et al., 2012 [73] Taiwan |
MDA-MB-231/Her2 Human |
Curcumin at 30 and 50 mM |
24 h | Not reported | Not reported | Flow cytometry Apoptosis occurred at a higher dosage (50 mM). |
None |
| Sun Xiao-Dong et al., 2012 [74] China |
MDA-MB-231 Human |
Curcumin at 10, 20, and 30 μmol/mL |
48 h | MTT assay The inhibitory effect on MDA-MB-231 cell proliferation peaked upon treatment with 30 μmol/mL curcumin (p < 0.01). |
Not reported | Flow cytometry Apoptosis control 2.76% and Curcumin 26.34%, 30 μmol/mL (p < 0.01). |
None |
| Wang Xet al., 2017 [76] China |
MCF-7 Human |
Curcumin [0 (with DMSO vehicle), 0.5, 1.0, 2.0, 5.0, and 10.0 µM] | 24, 48, and 72 h | MTT assay ↓ cell growth (treatment with 0, 0.5, 1.0, 2.0, 5.0, and 10.0 µM curcumin). |
Not reported | Flow cytometry Apoptotic cell death within 48 h upon treatment with 2 µM (p = 0.0021) and 5 µM (p = 0.0004) curcumin. |
None |
| Yang et al., 2017 a [76] China | MCF-7 Human |
Curcumin at 50 μm Nanostructured platform Micelle NPs (PPBV triblock copolymer) |
24 h | Not reported | Not reported | Flow cytometry Apoptotic cell death |
|
| Younesian et al., 2017 [80] Irã |
SKBR3 Human |
Curcumin at 2.5, 10, 15, 20, 25, and 30 μM | 24, 48, and 72 h | Not reported | Not reported | Flow cytometry Apoptosis: 4.37% with 0 μM, 27.46% with 5 μM, 64.98% with 10 μM, 75.90% with 15 μM, and 76.92% with 20 μM curcumin. |
None |
| Yu et al., 2021 [81] China |
4T1 Mouse |
Curcumin at 5, 10, and 15 μM |
24 h | Not reported | MTT assay ↓ of cell viability by 16% using 15 μg/mL curcumin |
Not reported | None |
| Zong et al., 2012 [84] China |
MCF-7 Human |
Curcumin at 10, 20, 50, and 100 μM | 48 h | MTT assay ↓ cell growth by 37%, 54%, and 73% using 20, 50, and 100 μM curcumin, respectively. |
Not reported | Not reported | None |
MTT assay, MTT Assay Protocol for Cell Viability and Proliferation, ↓: inhibition, ↑: activation.