Adenomatous Polyposis Coli Determines Sensitivity to Histone Deacetylase Inhibitor–Induced Apoptosis in Colon Cancer Cells
| العنوان: | Adenomatous Polyposis Coli Determines Sensitivity to Histone Deacetylase Inhibitor–Induced Apoptosis in Colon Cancer Cells |
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| المؤلفون: | Bin Guo, Xiangwei Huang |
| المصدر: | Cancer Research. 66:9245-9251 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2006. |
| سنة النشر: | 2006 |
| مصطلحات موضوعية: | Cancer Research, Programmed cell death, medicine.drug_class, Adenomatous polyposis coli, Survivin, Adenomatous Polyposis Coli Protein, Down-Regulation, Apoptosis, Hydroxamic Acids, Transfection, Inhibitor of Apoptosis Proteins, Glycogen Synthase Kinase 3, HT29 Cells, medicine, Humans, Enzyme Inhibitors, RNA, Small Interfering, Vorinostat, beta Catenin, Glycogen Synthase Kinase 3 beta, biology, Valproic Acid, Histone deacetylase inhibitor, Neoplasm Proteins, Histone Deacetylase Inhibitors, Oncology, Colonic Neoplasms, Cancer research, biology.protein, lipids (amino acids, peptides, and proteins), TCF Transcription Factors, Microtubule-Associated Proteins, Transcription Factor 7-Like 2 Protein, medicine.drug |
| الوصف: | Inhibitors of histone deacetylases (HDAC) inhibit malignant cell growth and induce apoptosis through unknown mechanisms. Here, we report that the expression status of adenomatous polyposis coli (APC) protein determines the relative sensitivity of colon cancer cells to HDAC inhibitor–induced apoptosis. HCA-7 cells (expressing wild-type β-catenin and APC proteins) are more sensitive to apoptosis induced by HDAC inhibitors valproic acid (VPA) and suberoylanilide hydroxamic acid than SW620 or HT-29 cells (both expressing mutant APC). When wild-type APC protein was expressed using an inducible expression system, HT-29 cells became sensitive to apoptosis in response to VPA. Conversely, knocking down of endogenous APC protein by small interfering RNA (siRNA) blocked VPA-induced apoptosis in HCA-7 cells. APC mediated VPA-induced apoptosis through down-regulation of survivin. The level of survivin protein decreased in HCA-7 and HT-29/APC cells, but not in SW620 and HT-29/β-Gal cells after VPA treatment. Whereas knocking down of survivin by siRNA sensitized SW620 cells to VPA-induced apoptosis, overexpression of survivin blocked VPA-induced apoptosis in HCA-7 cells. Down-regulation of survivin transcription occurred through changes in GSK-3β/β-catenin/Tcf-4 signaling molecules. VPA also induced proteasome-mediated degradation of survivin protein in HCA-7 cells. Furthermore, we have shown that APC mutation–mediated resistance to apoptosis can be overcome by cotreatment with Flavopiridol, which promotes survivin degradation. These results suggest that APC is a critical determinant of HDAC inhibitor–induced apoptosis in colon cancer cells and survivin is a potential target to enhance apoptotic response to HDAC inhibitors. (Cancer Res 2006; 66(18): 9245-51) |
| تدمد: | 1538-7445 0008-5472 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9c7e7ac94044e736e62e14945cf2196aTest https://doi.org/10.1158/0008-5472.can-06-0887Test |
| رقم الانضمام: | edsair.doi.dedup.....9c7e7ac94044e736e62e14945cf2196a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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