Regulation of Apoptosis Reduction in the Cisplatin-Resistant A431 Cell Line by Bcl-2 and CPP32
Cisplatin (cis-diamminedichloroplatinum(II), CDDP) is one of the most important chemotherapeutic agents; however, the mechanisms of resistance to this drug are still unknown. Recent reports have demonstrated that chemotherapy can induce apoptosis in some cancer cells, indicating that apoptosis may p...
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| Veröffentlicht in: | Chemotherapy (Basel) 2000-01, Vol.46 (1), p.69-76 |
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| creator | Mese, Hiroshi Sasaki, Akira Alcalde, Rafael E. Nakayama, Shuko Matsumura, Tomohiro |
| description | Cisplatin (cis-diamminedichloroplatinum(II), CDDP) is one of the most important chemotherapeutic agents; however, the mechanisms of resistance to this drug are still unknown. Recent reports have demonstrated that chemotherapy can induce apoptosis in some cancer cells, indicating that apoptosis may play a very important role in cancer therapy. Therefore, we used a CDDP-resistant cell line from the human epidermoid carcinoma cell line A431 to investigate whether the modulation of apoptosis influences CDDP resistance. In the CDDP-resistant cell, the cell cycle was not perturbed after CDDP treatment. DNA gel electrophoresis and ELISA of the CDDP-resistant cell showed reduced apoptosis when compared with A431 cells treated with CDDP. We determined the p53, Bcl-2, Bax and CPP32 protein levels by Western blotting. This analysis demonstrated a marked increase in Bcl-2 protein levels and a reduction in CPP32 protein levels in CDDP-resistant cells. Our results indicate that the reduction of apoptosis was one of the CDDP-resistant mechanisms, and that reduced apoptosis in CDDP-resistant cells was influenced by Bcl-2 and CPP32 proteins. |
| doi_str_mv | 10.1159/000007258 |
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Recent reports have demonstrated that chemotherapy can induce apoptosis in some cancer cells, indicating that apoptosis may play a very important role in cancer therapy. Therefore, we used a CDDP-resistant cell line from the human epidermoid carcinoma cell line A431 to investigate whether the modulation of apoptosis influences CDDP resistance. In the CDDP-resistant cell, the cell cycle was not perturbed after CDDP treatment. DNA gel electrophoresis and ELISA of the CDDP-resistant cell showed reduced apoptosis when compared with A431 cells treated with CDDP. We determined the p53, Bcl-2, Bax and CPP32 protein levels by Western blotting. This analysis demonstrated a marked increase in Bcl-2 protein levels and a reduction in CPP32 protein levels in CDDP-resistant cells. Our results indicate that the reduction of apoptosis was one of the CDDP-resistant mechanisms, and that reduced apoptosis in CDDP-resistant cells was influenced by Bcl-2 and CPP32 proteins.</description><identifier>ISSN: 0009-3157</identifier><identifier>EISSN: 1421-9794</identifier><identifier>DOI: 10.1159/000007258</identifier><identifier>PMID: 10601800</identifier><identifier>CODEN: CHTHBK</identifier><language>eng</language><publisher>Basel, Switzerland: Karger</publisher><subject>Antineoplastic agents ; Antineoplastic Agents - pharmacology ; Apoptosis - drug effects ; bcl-2-Associated X Protein ; Biological and medical sciences ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - pathology ; Caspase 3 ; Caspases - analysis ; Caspases - physiology ; CDC2 Protein Kinase - metabolism ; Cell Cycle - drug effects ; Cisplatin - pharmacology ; DNA Fragmentation - drug effects ; Drug Resistance, Neoplasm ; Experimental Chemotherapy ; General aspects ; Humans ; Medical sciences ; Pharmacology. 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Our results indicate that the reduction of apoptosis was one of the CDDP-resistant mechanisms, and that reduced apoptosis in CDDP-resistant cells was influenced by Bcl-2 and CPP32 proteins.</description><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>bcl-2-Associated X Protein</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Caspase 3</subject><subject>Caspases - analysis</subject><subject>Caspases - physiology</subject><subject>CDC2 Protein Kinase - metabolism</subject><subject>Cell Cycle - drug effects</subject><subject>Cisplatin - pharmacology</subject><subject>DNA Fragmentation - drug effects</subject><subject>Drug Resistance, Neoplasm</subject><subject>Experimental Chemotherapy</subject><subject>General aspects</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Pharmacology. 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Recent reports have demonstrated that chemotherapy can induce apoptosis in some cancer cells, indicating that apoptosis may play a very important role in cancer therapy. Therefore, we used a CDDP-resistant cell line from the human epidermoid carcinoma cell line A431 to investigate whether the modulation of apoptosis influences CDDP resistance. In the CDDP-resistant cell, the cell cycle was not perturbed after CDDP treatment. DNA gel electrophoresis and ELISA of the CDDP-resistant cell showed reduced apoptosis when compared with A431 cells treated with CDDP. We determined the p53, Bcl-2, Bax and CPP32 protein levels by Western blotting. This analysis demonstrated a marked increase in Bcl-2 protein levels and a reduction in CPP32 protein levels in CDDP-resistant cells. Our results indicate that the reduction of apoptosis was one of the CDDP-resistant mechanisms, and that reduced apoptosis in CDDP-resistant cells was influenced by Bcl-2 and CPP32 proteins.</abstract><cop>Basel, Switzerland</cop><pub>Karger</pub><pmid>10601800</pmid><doi>10.1159/000007258</doi><tpages>8</tpages></addata></record> |
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| ispartof | Chemotherapy (Basel), 2000-01, Vol.46 (1), p.69-76 |
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| subjects | Antineoplastic agents Antineoplastic Agents - pharmacology Apoptosis - drug effects bcl-2-Associated X Protein Biological and medical sciences Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - pathology Caspase 3 Caspases - analysis Caspases - physiology CDC2 Protein Kinase - metabolism Cell Cycle - drug effects Cisplatin - pharmacology DNA Fragmentation - drug effects Drug Resistance, Neoplasm Experimental Chemotherapy General aspects Humans Medical sciences Pharmacology. Drug treatments Proto-Oncogene Proteins - analysis Proto-Oncogene Proteins c-bcl-2 - biosynthesis Proto-Oncogene Proteins c-bcl-2 - physiology Tumor Cells, Cultured Tumor Suppressor Protein p53 - analysis |
| title | Regulation of Apoptosis Reduction in the Cisplatin-Resistant A431 Cell Line by Bcl-2 and CPP32 |
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