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
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  • Published online on: June 2, 2014     https://doi.org/10.3892/ijo.2014.2478
  • Pages: 782-794
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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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August-2014
Volume 45 Issue 2

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

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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