Table 1.
Synergic effects of EGCG in breast cancer models.
| Study | Treatment | Models | Outcomes | References |
|---|---|---|---|---|
| in vitro studies | ||||
| Cell viability by cell proliferation assay | 4-hydroxytamoxifen (1 μM) + 5–25 μM EGCG. 7 days |
MCF-7, 47D, MDA-MB-231 and HS578T | Decrease cell viability. Synergistic activity of EGCG in MDA-MB-231 cells at 25 μM. | [58] |
| Cell growth, apoptosis, and epigenetic regulation of transcriptional activity of DNA | Clofarabine/ EGCG 10 μM. 4 days |
MCF7 and MDA-MB-231 | Decrease cell growth with low toxicity. Increase in apoptosis and reactivation of DNA methylation-silenced tumor suppressor genes such as RARB. | [59] |
| Effects of Tapentadol on viability and migration | Tapentadol 1–80 μg/mL + EGCG 1–160 μM | MDA-MB-231 | Reduction of proliferation by impairing cell-cycle progression. Increase in apoptosis. | [60] |
| Inhibition insulin receptor substrate (IRS)/MAPK | 24 h of sunitinib and then 12 h with pulsed EGCG 0–50 μM | MCF-7, H460, and H1975, with PIK3CA mutations | Downregulation of insulin receptor substrate (IRS), suppressed mitogenic effects, and inhibition of IRS/MAPK/p-S6K1 signaling. | [61] |
| Reactivation of ERa by EGCG and histone deacetylase inhibitor | Trichostatin A (TSA) (100 ng/mL for 12 h) + 10 μM EGCG | MDA-MB-231 | Sensibilization of ERα-negative breast cancer cells to the activator 17β-estradiol (E2) and antagonist tamoxifen. | [62] |
| Effects of p53 gene silencing in conjunction with EGCG. | p53 siRNA 40 nmol + EGCG 24 h | Hs578T | Activation of pro-apoptotic and inhibition of anti-apoptotic genes, autophagy, and cell network formation. | [63] |
| Effects of EGCG and IIF in the EGFR inhibition | IIF 15 or 30 μM + 25 μg/mL EGCG by 24 h | MCF-7 and MDA-MB-231 | Inhibition of EGFR phosphorylation, invasion, and metastasis. | [64] |
| Synergism of SAHA and EGCG in TNBC cells | Suberoylanilide hydroxamic acid (SAHA) 25 mM + EGCG 100 mM, every 24 h/3 days | MDA-MB-157, MDA-MB-231, and HCC1806 | Increase apoptosis by decreasing cIAP2 and increasing pro-apoptotic caspase 7. Inhibition of cell migration. | [65] |
| Synergism of 5-aza 2’dC with EGCG | 5-aza 2′dC 5 µM+ EGCG 50 µM. 7 days |
MCF-7, MDA-MB 231 and MCF-10A | Synergic effects in cell growth inhibition by epigenetic mechanisms. | [66] |
| Evaluation of epigenetic induction of matrix metalloproteinase-3 | green tea polyphenols 10 µg/mL + EGCG 20 µM 24 h | MCF-7 and MDA-MB-231 | Activation of TIMP-3 and reduction of zeste homolog 2 (EZH2) and class I histone deacetylases (HDACs). | [67] |
| in vivo studies | ||||
| FLuc2 fusion with N-terminal 100-aa of Nrf2 and activation of Nrf2-ARE signaling | Oral cisplatin 5 mg/kg + EGCG 100 mg/kg. 11 days | MDA-MB231 tumor xenografts | Synergistic activity in vivo by Tumor size reduction in TNBC tumor xenografts. | [68] |
| Effects of EGCG on oral bioavailability of Tamoxifen | Tamoxifen (IV, 2 mg/kg and PO, 10 mg/kg), followed by EGCG (0.5, 3 and 10 mg/kg). | Male Sprague Dawley rats | Increase of bioavailability 1.48–1.77-fold of Tamoxifen in the presence of EGCG. | [69] |
| Evaluate angiogenesis and VEGF levels | EGCG single doses 4 h after sunitinib treatment | MCF-7 and H460 xenograft tumors | Downregulation of IRS-1 levels and suppressed mitogenic effects. Marked suppression of the IRS/MAPK/p-S6K1 signaling cascade. | [61] |