title: HY251, a novel decahydrocyclopenta[a]indene analog, induces apoptosis via tBid-mediated intrinsic pathway in human ovarian cancer PA-1 cells.
abstract: 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(ADP-ribose) 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.
authors.affiliation: Department of Pharmacy, College of Pharmacy, Hanyang University, Kyeonggi-do 426-791, Korea.
authors.forename: Hyewon
authors.initials: H
authors.lastname: Suh
authors.forename: Ko-woon
authors.initials: KW
authors.lastname: Choi
authors.forename: Myung Sic
authors.initials: MS
authors.lastname: Kim
authors.forename: Jeong Hyeon
authors.initials: JH
authors.lastname: Kim
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Noh
authors.forename: Moon-Hee
authors.initials: MH
authors.lastname: Sung
authors.forename: Chul-Hoon
authors.initials: CH
authors.lastname: Lee
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007192:Indenes / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014753:Vinyl Compounds / Q000494:pharmacology*
chemical_list: C539996:3-propyl-2-vinyl-1,2,3,3a,3b,6,7,7a,8,8a-decahydrocyclopenta(a)indene-3,3a,7a,8a-tetraol; D051023:BH3 Interacting Domain Death Agonist Protein; D007192:Indenes; D016159:Tumor Suppressor Protein p53; D014753:Vinyl Compounds; D011065:Poly(ADP-ribose) Polymerases; D053181:Caspase 8; D053453:Caspase 9