[Effect of up-regulation of S-AdoMet synthetase on taxol-induced apoptosis in human breast cancer cells].
OBJECTIVE: To investigate the gene regulation of taxol-induced apoptosis. METHODS: Northern blot hybridization, enzyme activity assay of S-AdoMet synthetase and flow cytometry were performed in the investigation of expression in the mRNA level and biological action of S-AdoMet synthetase in taxol-induced apoptosis in human breast cancer cell line (BCap 37). RESULTS: Up-regulation of S-AdoMet synthetase expression was resulted by taxol treatment and the expression peaked at 48 hours. Moreover, the up-regulation of S-AdoMet synthetase was associated with cytotoxicity of antimicrotubule agents including taxol and colchicine. Inhibition rate of S-AdoMet synthetase activity by 1% DMSO was 34% in taxol-treated cells and 14% in taxol-untreated cells compared to control groups, respectively. Posttreatment with 1% DMSO following pretreatment with individual antitumor agent for 3 hr promoted apoptotic cell death of taxol-, colchicine-, and adriamycin-treated BCap37 cells. CONCLUSION: The induction of apoptosis enhanced by post-treatment with DMSO in taxol-treated cells is probably linked to its inhibition on enzyme activity of S-AdoMet synthetase, suggesting that the increased expression of S-AdoMet synthetase possibly plays an important role in protecting cells from DNA fragmentation in taxol-induced apoptosis.