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Title: Beta catenin is degraded by both caspase-3 and proteasomal activity during resveratrol-induced apoptosis in HeLa cells in a GSK3β-independent manner
Authors: Ray, Mahan
Rai, Neha
Jana, Kuladip
Ghatak, Supratim
Basu, Arnab
Mustafi, Soumyajit Banerjee
Raha, Sanghamitra
Keywords: Resveratrol;HeLa;Apoptosis;β-Catenin;Caspase-3;GSK3β;Proteasomal degradation
Issue Date: Feb-2015
Publisher: NISCAIR-CSIR, India
Abstract: Increased activity of β-catenin, an important transcriptional activator for survival and proliferation-associated genes has been linked with many cancers. We examined whether β-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 β-catenin levels remained unchanged for 48 h during resveratrol exposure. However, extranuclear cell lysate β-catenin underwent a decrease at a late stage of apoptosis namely at 36-48 h. Alterations in the phosphorylation status of Akt/GSK3β were not observed during resveratrol-induced apoptosis. Furthermore, inhibition of GSK3β activity which is largely responsible for β-catenin degradation failed to influence β-catenin stability. However, inhibition of caspase-3 activity prevented the decline in β-catenin levels at 36-48 h of resveratrol exposure. Lactacystin, a proteosomal inhibitor also prevented the degradation of β-catenin by resveratrol. In conclusion, resveratrol induced apoptosis in HeLa cells in an Akt/GSK3β-independent manner and down-regulated β-catenin levels during apoptosis through action of caspase-3 and proteasomal degradation, independent of GSK3β-mediated phosphorylation.
Page(s): 7-13
ISSN: 0975-0959 (Online); 0301-1208 (Print)
Appears in Collections:IJBB Vol.52(1) [February 2015]

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