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Targeting Beta-Catenin Signaling to Induce Apoptosis in Human Breast Cancer Cells by Z-Guggulsterone and Gugulipid Extract of Ayurvedic Medicine Plant Commiphora Mukul

Targeting Beta-Catenin Signaling to Induce Apoptosis in Human Breast Cancer Cells by Z-Guggulsterone and Gugulipid Extract of Ayurvedic Medicine Plant Commiphora Mukul

Guoqin Jiang, Xiao Xiao, Yan Zeng, Kalyanam Nagabhushanam, Muhammed Majeed, Dong Xiao

BMC Complement Altern Med. 2013 Aug 3;13:203.

PMID: 23914993

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP39025235-A	Guggulsterone Z		39025-23-5	Price

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