TY - JOUR AB - Resveratrol is known to be an effective chemo­preventive phytochemical against multiple tumor cells. However, the increasing drug resistance avoids the cancer treatment in oral cavity cancer. In this study, we investigated the oral antitumor activity of resveratrol and its mechanism in cisplatin-resistant human oral cancer CAR cells. Our results demonstrated that resveratrol had an extremely low toxicity in normal oral cells and provoked autophagic cell death to form acidic vesicular organelles (AVOs) and autophagic vacuoles in CAR cells by acridine orange (AO) and monodansylcadaverine (MDC) staining. Either DNA fragmentation or DNA condensation occurred in resveratrol-triggered CAR cell apoptosis. These inhibitors of PI3K class III (3-MA) and AMP-activated protein kinase (AMPK) (compound c) suppressed the autophagic vesicle formation, LC3-II protein levels and autophagy induced by resveratrol. The pan-caspase inhibitor Z-VAD-FMK attenuated resveratrol-triggered cleaved caspase-9, cleaved caspase-3 and cell apoptosis. Resveratrol also enhanced phosphorylation of AMPK and regulated autophagy- and pro-apoptosis-related signals in resveratrol-treated CAR cells. Importantly, resveratrol also stimulated the autophagic mRNA gene expression, including Atg5, Atg12, Beclin-1 and LC3-II in CAR cells. Overall, our findings indicate that resveratrol is likely to induce autophagic and apoptotic death in drug-resistant oral cancer cells and might become a new approach for oral cancer treatment in the near future. AD - School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan, R.O.C. School of Pharmacy, China Medical University, Taichung 404, Taiwan, R.O.C. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan, R.O.C. Human Genetic Center, China Medical University Hospital, Taichung 404, Taiwan, R.O.C. Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan, R.O.C. Department of Pharmacy, Buddhist Tzu Chi General Hospital, Hualien 970, Taiwan, R.O.C. AU - Chang,Chao-Hsiang AU - Lee,Chao-Ying AU - Lu,Chi-Cheng AU - Tsai,Fuu-Jen AU - Hsu,Yuan-Man AU - Tsao,Je-Wei AU - Juan,Yu-Ning AU - Chiu,Hong-Yi AU - Yang,Jai-Sing AU - Wang,Ching-Chiung DA - 2017/03/01 DO - 10.3892/ijo.2017.3866 EP - 882 IS - 3 JO - Int J Oncol KW - resveratrol autophagic death apoptosis AMP-activated protein kinase cisplatin-resistant oral cancer cell PY - 2017 SN - 1019-6439 1791-2423 SP - 873 ST - Resveratrol-induced autophagy and apoptosis in cisplatin-resistant human oral cancer CAR cells: A key role of AMPK and Akt/mTOR signaling T2 - International Journal of Oncology TI - Resveratrol-induced autophagy and apoptosis in cisplatin-resistant human oral cancer CAR cells: A key role of AMPK and Akt/mTOR signaling UR - https://doi.org/10.3892/ijo.2017.3866 VL - 50 ER -