Targeting beta-Catenin signaling to induce apoptosis in human breast cancer cells by z-Guggulsterone and Gugulipid extract of Ayurvedic medicine plant Commiphora mukul

BMC Complementary and Alternative Medicine

Dong Xiao¹  Muhammed Majeed⁴  Kalyanam Nagabhushanam⁴  Yan Zeng¹  Xiao Xiao²  Guoqin Jiang³ 

[1] University of Pittsburgh Cancer Institute, University of Pittsburgh Medical College, University of Pittsburgh, Shadyside Medical Center, Suit G30, 5200 Centre Avenue, Pittsburgh, PA 15232, USA;Department of Urology, and University of Pittsburgh Medical College, University of Pittsburgh, Shadyside Medical Center, Suit G30, 5200 Centre Avenue, Pittsburgh PA 15232, USA;Department of General Surgery, The 2nd Affiliated Hospital of Soochow University, 1055 SanXian Road, Suzhou 215004, Jiangsu, China;Sabinsa Corporation, 20 Lake Drive, East Windsor, NJ 08520, USA

关键词: Breast cancer;    Beta-Catenin;    Apoptosis;    Guggulsterones;    Gugulipid;   

Others  :  1221043
DOI  :  10.1186/1472-6882-13-203

 received in 2013-04-03, accepted in 2013-07-29,  发布年份 2013

【 摘 要 】

Background

z-Guggulsterone (z-Gug) and Gugulipid (GL) have been used to treat a variety of ailments. We now report their anti-cancer effect and mechanism against human breast cancer.

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 efficacy and apoptosis inducing activity of GL. We determined the cellular and molecular mechanism of GL-inhibited breast cancer cell growth.

Results

GL significantly inhibited growth of MCF-7 and MDA-MB-231 cells with an IC₅₀~2 μM at pharmacologically relevant concentrations standardized to its major active constituent z-Gug. The GL-induced growth inhibition correlated with apoptosis induction as evidenced by an increase in cytoplasmic histone-associated DNA fragmentation and caspase 3 activity. The GL-induced apoptosis was associated with down-regulation of the β-Catenin signaling pathway. The decreased expression of Wnt/β-Catenin targeting genes, such as cyclin D1, C-myc and survivin, and the inhibition of the activity of the transcription factor (T-cell factor 4, TCF-4) were observed in GL-treated breast cancer cells. The GL treatment resulted in a significant reduction of β-Catenin /TCF-4 complex in both of the cancer cells. The GL-induced apoptotic cell death was significantly enhanced by RNA Interference of β-Catenin and TCF-4. On the other hand, the normal human mammary epithelial cell HMEC, compared with the human breast cancer cells, is significantly more resistant to growth inhibition and apoptosis induction by GL.

Conclusion

The present study indicates that the β-Catenin signaling pathway is the target for GL-induced growth inhibition and apoptosis in human breast cancer.

【 授权许可】

   
2013 Jiang et al.; licensee BioMed Central Ltd.

【 图 表 】

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