| Summary: | 碩士 === 中國醫藥大學 === 藥物化學研究所碩士班 === 98 === In this study, we screened the anticancer effect of a series synthetic carbozole derivative in human ovarian cancer cell line 2774, SKOV3 and breast cancer cell line MCF-7. Results showed that these synthetic compounds have growth inhibitory effects. Our results indicated that DSF-1g exerted the most potent inhibitory effects in human ovarian cancer cell line 2774. Cell viability analysis showed that DSF-1g inhibited cell growth and induced cell death in time- and dose-dependent manners. To search the mechanism of anti-proliferative effect of DSF-1g, cell cycle analysis was performed. DSF-1g treatment resulted in G2/M cell cycle arrest through down modulation of cyclin A and cdc25c. To investigate the mechanisms cell death underlying, 2774 cells treated with DSF-1g was studied by morphology, DAPI/TUNEL double stain and DNA gel electrophoresis. Results indicated DSF-1g treatment was related to the induction of apoptosis. Cells treated with cytotoxic concentrations of DSF-1g have increased apoptotic cell death via an increase in Bax/Bcl-2 ratio and proteolytic cleavage of procaspase 9, procaspase 3 and Poly (ADP-ribose) polymerase (PARP) and DNA fragmentation. The apoptosis triggered by DSF-1g was accompanied by the generation of reactive oxygen species. However, the apoptosis was p53- and Fas/FasL-independent. Taken together, these results suggested that DSF-1g-induced apoptosis was associated with ROS production and caspase cascade.
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