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

  • Authors:
    • 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
  • View Affiliations

  • Published online on: January 30, 2017     https://doi.org/10.3892/ijo.2017.3866
  • Pages: 873-882
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Abstract

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.
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March-2017
Volume 50 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Chang C, Lee C, Lu C, Tsai F, Hsu Y, Tsao J, Juan Y, Chiu H, Yang J, Wang C, Wang C, et al: Resveratrol-induced autophagy and apoptosis in cisplatin-resistant human oral cancer CAR cells: A key role of AMPK and Akt/mTOR signaling. Int J Oncol 50: 873-882, 2017
APA
Chang, C., Lee, C., Lu, C., Tsai, F., Hsu, Y., Tsao, J. ... Wang, C. (2017). Resveratrol-induced autophagy and apoptosis in cisplatin-resistant human oral cancer CAR cells: A key role of AMPK and Akt/mTOR signaling. International Journal of Oncology, 50, 873-882. https://doi.org/10.3892/ijo.2017.3866
MLA
Chang, C., Lee, C., Lu, C., Tsai, F., Hsu, Y., Tsao, J., Juan, Y., Chiu, H., Yang, J., Wang, C."Resveratrol-induced autophagy and apoptosis in cisplatin-resistant human oral cancer CAR cells: A key role of AMPK and Akt/mTOR signaling". International Journal of Oncology 50.3 (2017): 873-882.
Chicago
Chang, C., Lee, C., Lu, C., Tsai, F., Hsu, Y., Tsao, J., Juan, Y., Chiu, H., Yang, J., Wang, C."Resveratrol-induced autophagy and apoptosis in cisplatin-resistant human oral cancer CAR cells: A key role of AMPK and Akt/mTOR signaling". International Journal of Oncology 50, no. 3 (2017): 873-882. https://doi.org/10.3892/ijo.2017.3866