Inhibition of Tetrandrine on Epidermal Growth Factor-induced Cell Transformation and its Signal Transduction

Abstract

Background: The mouse epidermal JB6 cell system is a model for studying tumor promotion. We used the JB6 Cl 41 cell line to examine the mechanism of the anti-tumor-promoting effect of tetrandrine, an alkaloid isolated from Stephania tetrandra S Moore. Materials and Methods: The anti-tumor-promoting effect of tetrandrine was evaluated by assay of inhibition of epidermal growth factor (EGF)-induced transformation of JB6 Cl 41 cells in soft agar. The activity of activator protein-1 (AP-1), a transcription factor, was analyzed using the AP-1-dependent reporter assay. Phosphorylation of extracellular-signal regulated kinases (ERKs) and Akt, a pivotal effector of phosphatidylinositol 3-kinase (PI3K), was detected by Western blotting. Results: Tetrandrine significantly blocked EGF-induced cell transformation, attenuated EGF-induced AP-1 activation, and inhibited phosphorylation of ERKs, which regulates AP-1 activation. It also tended to suppress EGF-induced Akt phosphorylation. Conclusion: Our results indicate that tetrandrine inhibits EGF-induced transformation of JB6 cells by blocking the activation of ERKs, AP-1 and Akt.