title: Beta catenin is degraded by both caspase-3 and proteasomal activity during resveratrol-induced apoptosis in HeLa cells in a GSK3β-independent manner.
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.
authors.forename: Mahan
authors.initials: M
authors.lastname: Ray
authors.forename: Neha
authors.initials: N
authors.lastname: Rai
authors.forename: Kuladip
authors.initials: K
authors.lastname: Jana
authors.forename: Supratim
authors.initials: S
authors.lastname: Ghatak
authors.forename: Arnab
authors.initials: A
authors.lastname: Basu
authors.forename: Soumyajit Banerjee
authors.initials: SB
authors.lastname: Mustafi
authors.forename: Sanghamitra
authors.initials: S
authors.lastname: Raha
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006367:HeLa Cells; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D013267:Stilbenes; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D053148:Caspase 3; D046988:Proteasome Endopeptidase Complex; D000077185:Resveratrol