EFFECT OF UP-REGULATION OF S-ADOMET SYNTHETASE ON TAXOL-INDUCED APOPTOSIS IN HUMAN BREAST CANCER CELLS
Abstract
Objective: To investigate the gene regulation of taxolinduced 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 SAdoMet synthetase in taxoMnduced 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 taxoiuntreated cells compared to control groups, respectively. Posttreatment with 1% DMSO following pretreatment with individual antitumor agent for 3 hrs promoted apoptotic cell death of taxol-,colchicine-,and adriamycintreated 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 taxoMnduced 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 SAdoMet synthetase in taxoMnduced 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 taxoiuntreated cells compared to control groups, respectively. Posttreatment with 1% DMSO following pretreatment with individual antitumor agent for 3 hrs promoted apoptotic cell death of taxol-,colchicine-,and adriamycintreated 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 taxoMnduced apoptosis.