Beta catenin is degraded by both caspase-3 and proteasomal activity during resveratrol-induced apoptosis in HeLa cells in a GSK3ß-independent manner.
Indian J Biochem Biophys
; 52(1): 7-13, 2015 Feb.
Article
em En
| MEDLINE
| ID: mdl-26040106
ABSTRACT
Increased activity of ß-catenin, an important transcriptional activator for survival and proliferation-associated genes has been linked with many cancers. We examined whether ß-catenin is a target of resveratrol and whether its degradation contributes to the pro-apoptotic effects of resveratrol. HeLa cells were exposed to 60 µM resveratrol for 48 h. Apoptosis was confirmed by measurement of annexin V externalization, caspase-3 activation and DNA fragmentation. Induction of apoptosis was observed as early as 12 h, when both caspase-3 activation and PARP (poly ADP ribose polymerase) cleavage occurred. Nuclear ß-catenin levels remained unchanged for 48 h during resveratrol exposure. However, extranuclear cell lysate ß-catenin underwent a decrease at a late stage of apoptosis namely at 36-48 h. Alterations in the phosphorylation status of Akt/GSK3ß were not observed during resveratrol-induced apoptosis. Furthermore, inhibition of GSK3ß activity which is. largely responsible for ß-catenin degradation failed to influence ß-catenin stability. However, inhibition of caspase-3 activity prevented the decline in ß-catenin levels at 36-48 h of resveratrol exposure. Lactacystin, a proteosomal inhibitor also prevented the degradation of ß-catenin by resveratrol. In conclusion, resveratrol induced apoptosis in HeLa cells in an Akt/GSK3ß-independent manner and down-regulated ß-catenin levels during apoptosis through action of caspase-3 and proteasomal degradation, independent of GSK3ß-mediated phosphorylation.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estilbenos
/
Quinase 3 da Glicogênio Sintase
/
Beta Catenina
/
Caspase 3
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article