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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

  • Suh, Hyewon (Department of Pharmacy, College of Pharmacy, Hanyang University) ;
  • Choi, Ko-Woon (Department of Pharmacy, College of Pharmacy, Hanyang University) ;
  • Kim, Myung Sic (Department of Pharmacy, College of Pharmacy, Hanyang University) ;
  • Kim, Jeong Hyeon (Department of Pharmacy, College of Pharmacy, Hanyang University) ;
  • Noh, Sun Young (Department of Pharmacy, College of Pharmacy, Hanyang University) ;
  • Sung, Moon-Hee (Department of Advanced Fermentation Fusion Science and Technology, Kookmin University) ;
  • Lee, Chul-Hoon (Department of Pharmacy, College of Pharmacy, Hanyang University)
  • 투고 : 2012.09.07
  • 심사 : 2012.09.12
  • 발행 : 2012.11.28

초록

We previously isolated a novel compound, HY251, with the molecular structure of 3-propyl-2-vinyl-1,2,3,3a,3b,6,7,7a,8,8a-decahydrocyclopenta[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 $60{\mu}M$ 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(ADP-ribose) polymerase (PARP). Moreover, we found that this death event was also associated with the significant up-regulation 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.

키워드

참고문헌

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피인용 문헌

  1. Traditional uses, phytochemistry, pharmacology, toxicity and quality control of medicinal genus Aralia: A review vol.284, pp.None, 2012, https://doi.org/10.1016/j.jep.2021.114671