Inhibition of nuclear factor κB induces apoptosis following treatment with tumor necrosis factor α and an antioxidant in human prostate cancer cells
| Autor: | Darrell K. Murray, A. Wayne Meikle, Richard E. Swope, Kushlani Gunawardena |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
Cancer Research Proline Antineoplastic Agents Apoptosis Biology Inhibitor of apoptosis chemistry.chemical_compound Thiocarbamates Computer Graphics Tumor Cells Cultured Humans Tumor Necrosis Factor-alpha Cell growth NF-kappa B Prostatic Neoplasms Proteins NF-κB Molecular biology Neoplasm Proteins Oncology chemistry Cell culture Protein Biosynthesis Cancer cell Tumor necrosis factor alpha Transforming growth factor |
| Zdroj: | Cancer Detection and Prevention. 26:229-237 |
| ISSN: | 0361-090X |
| DOI: | 10.1016/s0361-090x(02)00061-2 |
| Popis: | Transforming growth factor beta-1 (TGFbeta-1) and tumor necrosis factor alpha (TNF-alpha), an activator of nuclear factor kappa B (NF-kappaB), modulate apoptosis and/or cell growth. This study was designed to investigate the activity of NF-kappaB and its regulation of inhibitor of apoptosis gene (c-IAP2) in two human prostate cancer cell lines, DU-145 (which is androgen unresponsive) and ALVA-101 (which is moderately androgen responsive). These cells were treated with and without various concentrations of a strong antioxidant, pyrrolidinedithiocarbamate (PDTC), and TNF-alpha at various time intervals. Following treatments, cell growth and apoptosis were determined by ELISA techniques. NF-kappaB activity was determined by electrophoretic mobility shift assay (EMSA), and c-IAP2 mRNA production was determined with Northern blot analysis. PDTC treatment significantly reduced cell growth up to 80% in both DU-145 and ALVA-101 cells. TNF-alpha and lower but not higher doses of PDTC combined demonstrated an additive inhibition of cell growth in both cell lines. Active NF-kappaB and c-IAP2 was blocked significantly following PDTC treatments, whereas treatments with TNF-alpha alone showed increased NF-kappaB activity and c-IAP2. However, when both PDTC and TNF-alpha were combined, nuclear presence of NF-kappaB and c-IAP2 were reduced significantly (P0.05) to levels observed with PDTC alone. In conclusion, the antioxidant, PDTC, appears to initiate apoptosis by blocking cytoplasmic NF-kappaB translocation to the nucleus where it normally activates the production of apoptosis-inhibitory proteins like c-IAP2. Both TNF-alpha and PDTC alone cause apoptosis and reduce cell growth, but their combined effects are additive in reducing cell growth of DU-145 and ALVA-101 human prostate cancer cells. |
| Databáze: | OpenAIRE |
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