Epigallocatechin gallate sensitizes cisplatin-resistant oral cancer CAR cell apoptosis and autophagy through stimulating AKT/STAT3 pathway and suppressing multidrug resistance 1 signaling

Abstract

Epigallocatechin gallate (EGCG) is a green tea polyphenol that presents anticancer activities in multiple cancer cells, but no available report was addressed for the underling molecular mechanism of cytotoxic impacts on drug-resistant oral squamous cell carcinoma cells. In the present study, the inhibitory effects of EGCG were experienced on cisplatin-resistant oral cancer CAR cells. EGCG inhibited cell viability in a time- and concentration-dependent manner by a sulforhodamine B (SRB) assay. EGCG induced CAR cell apoptosis and autophagy by 4',6-diamidino-2-phenylindole (DAPI) dye, acridine orange (AO) staining and green fluorescent protein (GFP)-tagged LC3B assay, respectively. EGCG also significantly enhanced caspase-9 and caspase-3 activities by caspase activity assay. EGCG markedly increased the protein levels of Bax, cleaved caspase-9, cleaved caspase-3, Atg5, Atg7, Atg12, Beclin-1, and LC3B-II, as well as significantly decreased the expression of Bcl-2, phosphorylated AKT (Ser473) and phosphorylation of STAT3 on Tyr705 by western blotting in CAR cells. Importantly, the protein and gene expression of multidrug resistance 1 (MDR1) were dose-dependently inhibited by EGCG. Overall, downregulation of MDR1 levels and alterations of AKT/STAT3 signaling contributed to EGCG-induced apoptosis and autophagy in CAR cells. Based on these results, EGCG has the potential for therapeutic effect on oral cancer and may be useful for long-term oral cancer prevention in the future. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 845-855, 2017.

SOX2OT variant 7 contributes to the synergistic interaction between EGCG and Doxorubicin to kill osteosarcoma via autophagy and stemness inhibition

“…At the same time, EGCG promoted the growth inhibition effect of antitumor drugs through autophagy regulation via activation of pro-apoptosis or pro-survival autophagy in cancer cells [3,29,30]. Based on the synergistic effect of EGCG and DOX on osteosarcoma growth inhibition, in second part of this study, it was confirmed that EGCG inhibited DOX induced pro-survival autophagy which would be one of the important molecular mechanism of synergistic effect of EGCG and DOX on osteosarcoma.…”

YC-1 induces G0/G1phase arrest and mitochondria-dependent apoptosis in cisplatin-resistant human oral cancer CAR cells

“…CAR cells are characterized by its stable resistance to cisplatin as previously described [1, 18, 85, 86]. The cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM) fortified with 10% fetal bovine serum (FBS), 100 U/ml penicillin, 100 μg/ml streptomycin, and 2 mM L-glutamine (Thermo Fisher Scientific) and were incubated at 37 °C with a humidified 5% CO2 air.…”

“…The cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM) fortified with 10% fetal bovine serum (FBS), 100 U/ml penicillin, 100 μg/ml streptomycin, and 2 mM L-glutamine (Thermo Fisher Scientific) and were incubated at 37 °C with a humidified 5% CO2 air. The cisplatin-resistant CAR cells were constantly cultured in medium containing 80 μM cisplatin unless otherwise indicated [1, 18, 85, 86]. …”

“…The number of cancer death reports was 46, 829 (28, 776 in men and 18, 053 in women), accounting for 28.6% of the total number of deaths. The death rate was 199.6 per 100, 000 population, increased by 1.3% from 2013 to 2014 [1, 2]. Oral cancer is the fifth leading cause of cancer death in Taiwan.…”

“…Oral cancer is the fifth leading cause of cancer death in Taiwan. The death rate of oral cancer was 11.4 per 100, 000 population [1, 2]. In Taiwan, the major risk factors of oral cancer are betel nut chewing [3–6], smoking [7], alcohol consumption [4, 8], inflammation [9, 10] and human papilloma virus (HPV) infection [11, 12].…”