HY251, a novel decahydrocyclopenta[a]indene analog, induces apoptosis via tBid-mediated intrinsic pathway in human ovarian cancer PA-1 cells.
J Microbiol Biotechnol
; 22(11): 1591-5, 2012 Nov.
Article
em En
| MEDLINE
| ID: mdl-23124353
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
/
Compostos de Vinila
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Transdução de Sinais
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Apoptose
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Proteína Agonista de Morte Celular de Domínio Interatuante com BH3
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Indenos
Limite:
Female
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Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article