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Resveratrol-induced p53-independent apoptosis of human nasopharyngeal carcinoma cells is correlated with the downregulation of ΔNp63
- Source :
- Cancer Gene Therapy. 17:872-882
- Publication Year :
- 2010
- Publisher :
- Springer Science and Business Media LLC, 2010.
-
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.
- Subjects :
- Cancer Research
Programmed cell death
viruses
Down-Regulation
Apoptosis
Biology
medicine.disease_cause
Downregulation and upregulation
Cell Line, Tumor
Stilbenes
medicine
Anticarcinogenic Agents
Humans
Gene silencing
RNA, Small Interfering
Molecular Biology
Cell Proliferation
Tumor Suppressor Proteins
Carcinoma
virus diseases
Nasopharyngeal Neoplasms
Transfection
respiratory system
medicine.disease
Nasopharyngeal carcinoma
Resveratrol
Cancer cell
Trans-Activators
Cancer research
Molecular Medicine
Tumor Suppressor Protein p53
Carcinogenesis
Transcription Factors
Subjects
Details
- ISSN :
- 14765500 and 09291903
- Volume :
- 17
- Database :
- OpenAIRE
- Journal :
- Cancer Gene Therapy
- Accession number :
- edsair.doi.dedup.....5222be4c1b622c0d80bcf5add70d5d60