[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.


CONCLUSIONS
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.
Cancer Institute, Zhejiang Medical University, Hangzhou.
L
L
Chen
S
S
Zheng
W
W
Fan
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology*; D006801:Humans; D008716:Methionine Adenosyltransferase / Q000096:biosynthesis* / Q000235:genetics; D017239:Paclitaxel / Q000494:pharmacology*; D000091402:Prohibitins; D012333:RNA, Messenger / Q000235:genetics; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000972:Antineoplastic Agents, Phytogenic; C000717331:PHB2 protein, human; D000091402:Prohibitins; D012333:RNA, Messenger; D008716:Methionine Adenosyltransferase; D017239:Paclitaxel