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KMID : 0545120120220111591
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Journal of Microbiology and Biotechnology
2012 Volume.22 No. 11 p.1591 ~ p.1595
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HY251, a Novel Decahydrocyclopenta[a]indene Analog, Induces Apoptosis via tBid-Mediated Intrinsic Pathway in Human Ovarian Cancer PA-1 Cells
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Suh Hye-Won
Choi Ko-Woon
Kim Myung-Sic
Kim Jeong-Hyeon
Noh Sun-Young
Sung Moon-Hee
Lee Chul-Hoon
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Abstract
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We previously isolated a novel compound, HY251, with the molecular structure of 3-propyl-2-vinyl-1,2,3,3a,3b,6,7,7a,8,8adecahydrocyclopenta[ a]indene-3,3a,7a,8a-tetraol from the roots of Aralia continentalis. The current study was designed to evaluate the detailed molecular mechanisms underlying the apoptotic induction by HY251 in human ovarian cancer PA-1 cells. TUNEL assay and Western blot analyses revealed an appreciable apoptotic induction in PA-1 cells treated with 60 μM of HY251 for 24 h. This apoptotic induction was associated with caspase-8-dependent Bid cleavage, which in turn resulted in the formation of pro-apoptotic truncated Bid (tBid), and activation of caspase-9 and -3, as well as the cleavage of poly(ADPribose) polymerase (PARP). Moreover, we found that this death event was also associated with the significant upregulation and activation of the p53 tumor-suppressor protein through phosphorylation at Ser15. Therefore, we suggest that HY251 may be a potent cancer chemotherapeutic candidate for the treatment of ovarian cancer.
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KEYWORD
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Aralia continentalis, apoptotic induction, tBid, cytochrome c, PA-1 cells
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