Caffeic acid phenethyl ester accumulates beta-catenin through GSK-3 beta and participates in proliferation through mTOR in C2C12 cells

Abstract

Aim: The aim of this study is to characterize the roles of caffeic acid phenethyl ester (CAPE) in the skeletal muscle cells. Main methods: We performed immunoblotting assay using various phosphorylation specific antibodies. Key findings: We found that CAPE induces rapid and transient phosphorylation of glycogen synthase kinase (GSK)-3 beta in a phosphoinositide 3-kinase (PI3K)-dependent manner. CAPE also decreases phosphorylation of beta-catenin, ultimately leading to beta-catenin accumulation. In addition, we demonstrated that CAPE activated the mammalian target of rapamycin (mTOR)-p70 S6 ribosomal kinase (S6K) and also stimulated extracellular signal-regulated kinase (ERK). The inhibition of mTOR blocked CAPE-induced ERK phosphorylation. Significance: Our results suggest that CAPE may act through beta-catenin accumulation via stimulation of GSK-3 beta and may also participate in cellular proliferation through the mTOR-ERK pathway. (C) 2009 Elsevier Inc. All rights reserved.