University of Pittsburgh, USA
Dr.Dong Xiao is a professor at University of Pittsburg, USA.
1Department of Urology, University of Pittsburgh, USA 2Department of General Surgery, The Second Affiliated Hospital of Soochow University, China Introduction: Gugulipid (GL), extract of Indian Ayurvedic medicinal plant Commiphora mukul, has been used to treat a variety of ailments. We now report anti-cancer eff ect and mechanism of GL against human breast cancer cells. Methods: Using the human estrogen receptor-positive (MCF-7) and triple-negative (MDA-MB-231) breast cancer cells as well as the normal human mammary epithelial cell line (HMEC), we evaluated the anti-breast-cancer effi cacy of GL. We measured the activity of GL on apoptosis inducing. Finally, we determined the cellular and molecular mechanism of GL-inhibited breast cancer cell growth. Results: Treatment with GL signifi cantly inhibited viability of human breast cancer cell line MCF-7 and MDA-MB-231 cells with an IC50~2 μM (24 h treatment) at pharmacologically relevant concentrations standardized to its major active constituent z-guggulsterone. Th e GL-induced growth inhibition correlated with apoptosis induction as evidenced by an increase in cytoplasmic histone-associated DNA fragmentation and caspase 3 activity. Interestingly, a normal human mammary epithelial cell line HMEC is signifi cantly more resistant to growth inhibition and apoptosis induction by GL. Th e GL-induced apoptosis was associated with down-regulation of β-Catenin signaling pathway. Th e decrease of Wnt/β-Catenin targeting genes, such as cyclin D1, C-myc and inhibition of transcription factor (T-cell factor4, TCF4) was observed in GL-treated breast cancer cells. Th e GL treatment caused apoptotic cell death was signifi cantly enhanced by RNA Interference of β-Catenin and TCF-4. Conclusion: the present study indicates that β-Catenin signaling pathway is the target for GL-induced the growth inhibition and apoptosis induction in human breast cancer. This investigation was supported by USPHS grant R21 CA143104 and RO1-CA157477, awarded by the National Cancer Institute.