Epigallocatechin gallate sensitizes cisplatin-resistant oral cancer CAR cell apoptosis and autophagy through stimulating AKT/STAT3 pathway and suppressing multidrug resistance 1 signaling
| Autor: | Chien Han Yuan, Fu‑An Chen, Chi Cheng Lu, Ni Na Chiang, Fuu Jen Tsai, Jo Hua Chiang, Chi‑Ting Horng, Yuan-Man Hsu, Chiu Fang Lee, Jai Sing Yang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Health Toxicology and Mutagenesis ATG5 food and beverages Caspase 3 General Medicine Management Monitoring Policy and Law Biology Epigallocatechin gallate Toxicology complex mixtures Molecular biology ATG12 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine chemistry Apoptosis 030220 oncology & carcinogenesis Cancer research sense organs Viability assay DAPI Protein kinase B |
| Zdroj: | Environmental Toxicology. 32:845-855 |
| ISSN: | 1520-4081 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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