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Article

The novel pterostilbene derivative ANK-199 induces autophagic cell death through regulating PI3 kinase class III/beclin 1/Atg‑related proteins in cisplatin‑resistant CAR human oral cancer cells

  • Authors:
    • Min-Tsang Hsieh
    • Hao-Ping Chen
    • Chi-Cheng Lu
    • Jo-Hua Chiang
    • Tian-Shung Wu
    • Daih-Huang Kuo
    • Li-Jiau Huang
    • Sheng-Chu Kuo
    • Jai-Sing Yang
  • View Affiliations / Copyright

    Affiliations: School of Pharmacy, China Medical University, Taichung 404, Taiwan, R.O.C., Department of Biochemistry, Tzu Chi University, Hualien 970, Taiwan, R.O.C., Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 402, Taiwan, R.O.C., Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan, R.O.C., Department of Pharmacy and Graduate Institute of Pharmaceutical Technology, Tajen University, Pingtung 907, Taiwan, R.O.C., Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung 404, Taiwan, R.O.C., Department of Pharmacology, China Medical University, Taichung 404, Taiwan, R.O.C.
  • Pages: 782-794
    |
    Published online on: June 2, 2014
       https://doi.org/10.3892/ijo.2014.2478
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Abstract

Pterostilbene is an effective chemopreventive agent against multiple types of cancer cells. A novel pterostilbene derivative, ANK-199, was designed and synthesized by our group. Its antitumor activity and mechanism in cisplatin-resistant CAR human oral cancer cells were investigated in this study. Our results show that ANK-199 has an extremely low toxicity in normal oral cell lines. The formation of autophagic vacuoles and acidic vesicular organelles (AVOs) was observed in the ANK-199-treated CAR cells by monodansylcadaverine (MDC) and acridine orange (AO) staining, suggesting that ANK-199 is able to induce autophagic cell death in CAR cells. Neither DNA fragmentation nor DNA condensation was observed, which means that ANK-199-induced cell death is not triggered by apoptosis. In accordance with morphological observation, 3-MA, a specific inhibitor of PI3K kinase class III, can inhibit the autophagic vesicle formation induced by ANK-199. In addition, ANK-199 is also able to enhance the protein levels of autophagic proteins, Atg complex, beclin 1, PI3K class III and LC3-II, and mRNA expression of autophagic genes Atg7, Atg12, beclin 1 and LC3-II in the ANK-199-treated CAR cells. A molecular signaling pathway induced by ANK-199 was therefore summarized. Results presented in this study show that ANK-199 may become a novel therapeutic reagent for the treatment of oral cancer in the near future (patent pending).
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Spandidos Publications style
Hsieh M, Chen H, Lu C, Chiang J, Wu T, Kuo D, Huang L, Kuo S and Yang J: The novel pterostilbene derivative ANK-199 induces autophagic cell death through regulating PI3 kinase class III/beclin 1/Atg‑related proteins in cisplatin‑resistant CAR human oral cancer cells. Int J Oncol 45: 782-794, 2014.
APA
Hsieh, M., Chen, H., Lu, C., Chiang, J., Wu, T., Kuo, D. ... Yang, J. (2014). The novel pterostilbene derivative ANK-199 induces autophagic cell death through regulating PI3 kinase class III/beclin 1/Atg‑related proteins in cisplatin‑resistant CAR human oral cancer cells. International Journal of Oncology, 45, 782-794. https://doi.org/10.3892/ijo.2014.2478
MLA
Hsieh, M., Chen, H., Lu, C., Chiang, J., Wu, T., Kuo, D., Huang, L., Kuo, S., Yang, J."The novel pterostilbene derivative ANK-199 induces autophagic cell death through regulating PI3 kinase class III/beclin 1/Atg‑related proteins in cisplatin‑resistant CAR human oral cancer cells". International Journal of Oncology 45.2 (2014): 782-794.
Chicago
Hsieh, M., Chen, H., Lu, C., Chiang, J., Wu, T., Kuo, D., Huang, L., Kuo, S., Yang, J."The novel pterostilbene derivative ANK-199 induces autophagic cell death through regulating PI3 kinase class III/beclin 1/Atg‑related proteins in cisplatin‑resistant CAR human oral cancer cells". International Journal of Oncology 45, no. 2 (2014): 782-794. https://doi.org/10.3892/ijo.2014.2478
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Spandidos Publications style
Hsieh M, Chen H, Lu C, Chiang J, Wu T, Kuo D, Huang L, Kuo S and Yang J: The novel pterostilbene derivative ANK-199 induces autophagic cell death through regulating PI3 kinase class III/beclin 1/Atg‑related proteins in cisplatin‑resistant CAR human oral cancer cells. Int J Oncol 45: 782-794, 2014.
APA
Hsieh, M., Chen, H., Lu, C., Chiang, J., Wu, T., Kuo, D. ... Yang, J. (2014). The novel pterostilbene derivative ANK-199 induces autophagic cell death through regulating PI3 kinase class III/beclin 1/Atg‑related proteins in cisplatin‑resistant CAR human oral cancer cells. International Journal of Oncology, 45, 782-794. https://doi.org/10.3892/ijo.2014.2478
MLA
Hsieh, M., Chen, H., Lu, C., Chiang, J., Wu, T., Kuo, D., Huang, L., Kuo, S., Yang, J."The novel pterostilbene derivative ANK-199 induces autophagic cell death through regulating PI3 kinase class III/beclin 1/Atg‑related proteins in cisplatin‑resistant CAR human oral cancer cells". International Journal of Oncology 45.2 (2014): 782-794.
Chicago
Hsieh, M., Chen, H., Lu, C., Chiang, J., Wu, T., Kuo, D., Huang, L., Kuo, S., Yang, J."The novel pterostilbene derivative ANK-199 induces autophagic cell death through regulating PI3 kinase class III/beclin 1/Atg‑related proteins in cisplatin‑resistant CAR human oral cancer cells". International Journal of Oncology 45, no. 2 (2014): 782-794. https://doi.org/10.3892/ijo.2014.2478
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