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

The aim of this study is to characterize the roles of caffeic acid phenethyl ester (CAPE) in the skeletal muscle cells.We performed immunoblotting assay using various phosphorylation specific antibodies.We found that CAPE induces rapid and transient phosphorylation of glycogen synthase kinase (GSK)-3beta 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.Our results suggest that CAPE may act through beta-catenin accumulation via stimulation of GSK-3beta and may also participate in cellular proliferation through the mTOR-ERK pathway.