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Obstet Gynecol Sci > Volume 54(2); 2011 > Article
Korean Journal of Obstetrics & Gynecology 2011;54(2):86-92.
DOI: https://doi.org/10.5468/KJOG.2011.54.2.86    Published online February 1, 2011.
Apoptotic effect of NV-196, an isofl avone derivative, in epithelial ovarian cancer cells.
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.
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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