Resveratrol-induced autophagy and apoptosis in cisplatin-resistant human oral cancer CAR cells: A key role of AMPK and Akt/mTOR signaling

Chao Hsiang Chang, Chao Ying Lee, Chi Cheng Lu, Fuu Jen Tsai, Yuan Man Hsu, Je Wei Tsao, Yu Ning Juan, Hong Yi Chiu, Jai Sing Yang, Ching Chiung Wang

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151 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)873-882
Number of pages10
JournalInternational Journal of Oncology
Issue number3
Publication statusPublished - Mar 1 2017


  • AMP-Activated protein kinase
  • Apoptosis
  • Autophagic Death
  • Cisplatin-resistant oral cancer cell
  • Resveratrol

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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