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KMID : 0358420110540020086
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Korean Journal of Obstetrics and Gynecology
2011 Volume.54 No. 2 p.86 ~ p.92
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APOPTOTIC EFFECT OF NV-196, AN ISOFLAVONE DERIVATIVE, IN EPITHELIAL OVARIAN CANCER CELLS
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Suh Dong-Soo
Joo Jong-Kil
Kim Seong-Chol
Lee Dong-Hyung
Yi Woo-Hee
Yoon Man-Soo
Kim Ki-Hyung
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Abstract
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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 μg/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.
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KEYWORD
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Epithelial ovarian cancer, Isofl avone, NV-196, Paclitaxel, Carboplatin
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