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Resveratrol-induced p53-independent apoptosis of human nasopharyngeal carcinoma cells is correlated with the downregulation of ΔNp63

Cancer Gene Therapy volume 17, pages 872–882 (2010)Cite this article

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Abstract

ΔNp63, the N-terminal truncated isoform of p63, has been found to be overexpressed in several human epithelial cancers, including nasopharyngeal carcinomas (NPCs), suggesting a function in carcinogenesis. Trans-resveratrol (RSV) has been shown to exert proapoptotic activities through a p53-dependent or p53-independent pathway in various cancer cells. However, the effects of RSV on NPC are still unexplored. In this study, we investigated the apoptotic effects of RSV on ΔNp63-overexpressing NPC cell lines. We showed that RSV (12–100 μ) induced dose-dependent growth suppression, cell-cycle arrest in the S phase and caspase-dependent apoptosis in NPC-TW076 and NPC-TW039 cells. The RSV effect was accompanied by the downregulation of ΔNp63 and the upregulation of p53 protein in a dose-dependent manner. By using small-interfering RNA (siRNA) technology, we found that the targeted silencing of ΔNp63 induced apoptosis and sensitized the NPC cells to RSV-induced apoptosis through caspase-3 activation, whereas suppression of p53 by siRNA did not inhibit RSV-induced apoptosis. Furthermore, transfection with p53 siRNA or pretreatment with caspase inhibitors (Z-VAD-fmk or Z-DEVD-fmk) had no influence on the RSV downregulation of ΔNp63. Interestingly, ecoptic expression of ΔNp63 did not significantly block RSV-induced cell death and was also downregulated after RSV treatment. Downregulation of ΔNp63 by RSV was shown to occur at the mRNA transcript and post-translational levels. Importantly, RSV enhanced chemotheraptic drug-induced apoptosis in NPC and two human carcinoma cell lines, HT1376 and Hep3B cells. These results suggested that ΔNp63, but not p53, is a molecular target of RSV-induced apoptosis and the regulation of ΔNp63 expression by RSV may provide a therapeutic effect of RSV in human NPC.

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Acknowledgements

This work was supported by funding from the Chang Gung Memorial Hospital SE Chow (CMRPD 170181) and by a grant from National Science Council to JS Wang (NSC 97-2314-B-182-003-MY3).

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Authors and Affiliations

  1. Center for General Studies, Chang Gung University, Taoyuan, Taiwan, ROC

    S-E Chow & W-S Chen

  2. Department of Rehabilitation Science, Chang Gung University, Taoyuan, Taiwan, ROC

    J-S Wang & Y-W Chen

  3. Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan, ROC

    S-F Chuang

  4. Department of Traditional Chinese Medicine, Chang-Gung University, Taoyuan, Taiwan, ROC

    Y-L Chang

  5. Department of Physiology, Chang Gung University, Taoyuan, Taiwan, ROC

    W-K Chu

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  1. S-E Chow
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Correspondence to S-E Chow.

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Chow, SE., Wang, JS., Chuang, SF. et al. Resveratrol-induced p53-independent apoptosis of human nasopharyngeal carcinoma cells is correlated with the downregulation of ΔNp63. Cancer Gene Ther 17, 872–882 (2010). https://doi.org/10.1038/cgt.2010.44

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