| Resveratrol-induced p53-independent apoptosis of human nasopharyngeal carcinoma cells is correlated with the downregulation of ΔNp63. | |
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MedLine Citation:
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PMID: 20725098 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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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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Authors:
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S-E Chow; J-S Wang; S-F Chuang; Y-L Chang; W-K Chu; W-S Chen; Y-W Chen |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-20 |
Journal Detail:
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Title: Cancer gene therapy Volume: 17 ISSN: 1476-5500 ISO Abbreviation: Cancer Gene Ther. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-15 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9432230 Medline TA: Cancer Gene Ther Country: England |
Other Details:
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Languages: eng Pagination: 872-82 Citation Subset: IM |
Affiliation:
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Center for General Studies, Chang Gung University, Taoyuan, Taiwan, ROC. chowse@mail.cgu.edu.tw |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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