| Apoptotic effect of NV-196, an isofl avone derivative, in epithelial ovarian cancer cells. |
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Dong Soo Suh, Jong Kil Joo, Seung Chul Kim, Dong Hyung Lee, Woo Hee Yi, Man Soo Yoon, Ki Hyung Kim |
1Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Busan, Korea. ghkim@pusan.ac.kr
2Department of Obstetrics and Gynecology, Busan St. Mary's Medical Center, Busan, Korea. |
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| Abstract |
OBJECTIVE
The objectives of this study were to determine the efficacy of NV-196, a synthetic isoflavone derivative, as a chemosensitizer in chemoresistant CP70 and R182 epithelial ovarian cancer (EOC) cells and to characterize the mechanism behind its sensitizing effect. METHODS: EOC cells were treated with tenfold dilutions of NV-196 (0.1 to 10 microg/mL) for 24 and 48 hours. Cell viability was determined by the CellTiter 96 AQueous One Solution Cell Proliferation Assay. Apoptosis was assessed by Caspase-Glo assays and apoptotic cascade X-linked inhibitor of apoptosis protein (XIAP), caspase-2 and Bid were characterized by Western blot analyses. RESULTS: As a monotherapy, NV-196 showed decreased cell viability in a time- and dose-dependent manner in both CP70 and R182 cells. A signifi cant increase in caspase-3 activity was observed in both cells. Caspase-8 and -9 activation were also observed. Western blots demonstrated Bid and caspase-2 activation and cleavage of XIAP. NV-196 enhances the cytotoxic effects of carboplatin and paclitaxel. CONCLUSION: NV-196 induces cell death through the induction of apoptosis. Pretreatment with NV-196 may sensitize the ovarian cancer cells to carboplatin or paclitaxel. NV-196 may act as a chemosensitizing agent in epithelial ovarian cancer cells. |
| Key Words:
Epithelial ovarian cancer, Isofl avone, NV-196, Paclitaxel, Carboplatin |
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