Gossypol induces apoptosis in human PC-3 prostate cancer cells by modulating caspase-dependent and caspase-independent cell death pathways
| Autor: | Min Ji, Manchao Zhang, Brian N. Griffith, Hongpeng Liu, Q. Quentin Li, Zhenkun Tian |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Male
bcl-X Protein Apoptosis Adenocarcinoma Cysteine Proteinase Inhibitors Mitochondrion General Biochemistry Genetics and Molecular Biology Amino Acid Chloromethyl Ketones chemistry.chemical_compound Cell Line Tumor Proto-Oncogene Proteins Humans General Pharmacology Toxicology and Pharmaceutics Caspase Cell Proliferation bcl-2-Associated X Protein Bcl-2-Like Protein 11 Dose-Response Relationship Drug biology Cell growth Contraceptive Agents Male Gossypol Apoptosis Inducing Factor Membrane Proteins Prostatic Neoplasms General Medicine Caspase Inhibitors Cell biology Cytosol chemistry Cell culture Caspases biology.protein Apoptosis-inducing factor Apoptosis Regulatory Proteins Protein Binding |
| Zdroj: | Life Sciences. 80:767-774 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/j.lfs.2006.11.004 |
| Popis: | The rate of gossypol-induced apoptosis does not correlate very well with the same dose of gossypol-induced cell growth inhibition, indicating an anti-proliferative effect of gossypol. Using a co-immunoprecipitation assay, it was observed that the level of Bcl-X(L) protein bound to Bax was clearly lower than that of Bcl-2 protein at 5 micro M of gossypol treatment, and the level of Bim protein bound to Bcl-X(L) was lowered at 20 micro M of gossypol treatment for 24 h, implicating that gossypol inhibits the heterodimerization of Bcl-X(L) with Bax and Bim. Gossypol-induced apoptosis is partly suppressed by as low as 0.5 micro M, but not abolished by as high as 50 micro M of a broad range caspase inhibitor, Z-VAD-FMK, suggesting that gossypol-induced apoptosis is both caspase-dependent and -independent. Furthermore, the release of apoptosis inducing factor (AIF), which triggers caspase-independent apoptosis, from mitochondria to cytosol was observed in PC-3 cells exposed to gossypol treatment. In conclusion, gossypol inhibits the proliferation and induces apoptosis in PC-3 cells. Gossypol-induced apoptosis is, at least, through inhibiting the heterodimerization of Bcl-X(L)/Bcl-2 with pro-apoptosis molecules, followed by a caspase-dependent and -independent process which involves the release of AIF from the mitochondria to cytosol. |
| Databáze: | OpenAIRE |
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