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Synthesis and inhibitory effect of 10-chlorocanthin-6-one on ovarian cancer HO8910PM cells.
Biotechnology Letters 2018 January
OBJECTIVE: To synthesize and determine the antitumor activity of 10-chlorocanthin-6-one in ovarian cancer HO8910PM cells.
RESULTS: Among the synthesized canthin-6-one analogs, 10-chlorocanthin-6-one was the most cytotoxic (IC50 = 4.9 μM), as demonstrated by a dose-dependent cytotoxicity assay. Moreover, 10-chlorocanthin-6-one induced apoptosis through the activation of poly(ADP-ribose) polymerase and caspase-3 cleavage, upregulation of Bcl-2, and downregulation of Bim, x-linked inhibitor of apoptosis protein (XIAP), and survivin in HO8910PM cells. Furthermore, Bim RNA, upregulated in a concentration-dependent manner, and knockdown of Bim via short-hairpin RNAs attenuated the inhibitory effects of 10-chlorocanthin-6-one on HO8910PM cell growth.
CONCLUSIONS: 10-Chlorocanthin-6-one inhibits cell proliferation and induces apoptosis in H08910PM cells. The underlying molecular mechanisms of 10-chlorocanthin-6-one include activation of the Bim-mediated mitochondrial apoptotic pathway via upregulation of Bim and downregulation of Bcl-2, XIAP, and survivin. These data suggest that Bim is a potential target of 10-chlorocanthin-6-one, further demonstrating its potential use in the prevention and treatment of ovarian cancer.
RESULTS: Among the synthesized canthin-6-one analogs, 10-chlorocanthin-6-one was the most cytotoxic (IC50 = 4.9 μM), as demonstrated by a dose-dependent cytotoxicity assay. Moreover, 10-chlorocanthin-6-one induced apoptosis through the activation of poly(ADP-ribose) polymerase and caspase-3 cleavage, upregulation of Bcl-2, and downregulation of Bim, x-linked inhibitor of apoptosis protein (XIAP), and survivin in HO8910PM cells. Furthermore, Bim RNA, upregulated in a concentration-dependent manner, and knockdown of Bim via short-hairpin RNAs attenuated the inhibitory effects of 10-chlorocanthin-6-one on HO8910PM cell growth.
CONCLUSIONS: 10-Chlorocanthin-6-one inhibits cell proliferation and induces apoptosis in H08910PM cells. The underlying molecular mechanisms of 10-chlorocanthin-6-one include activation of the Bim-mediated mitochondrial apoptotic pathway via upregulation of Bim and downregulation of Bcl-2, XIAP, and survivin. These data suggest that Bim is a potential target of 10-chlorocanthin-6-one, further demonstrating its potential use in the prevention and treatment of ovarian cancer.
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