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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

Jiang, G and Xiao, X and Zeng, Y and Nagabhushanam, K and Majeed, M and Xiao, D (2013) 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, 13.

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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. © 2013 Jiang et al.; licensee BioMed Central Ltd.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Jiang, G
Xiao, X
Zeng, Y
Nagabhushanam, K
Majeed, M
Xiao, D
Centers: Other Centers, Institutes, or Units > Pittsburgh Cancer Institute
Date: 3 August 2013
Date Type: Publication
Journal or Publication Title: BMC Complementary and Alternative Medicine
Volume: 13
DOI or Unique Handle: 10.1186/1472-6882-13-203
Schools and Programs: School of Medicine > Urology
Refereed: Yes
Date Deposited: 02 Dec 2016 14:58
Last Modified: 27 Jan 2019 04:55
URI: http://d-scholarship.pitt.edu/id/eprint/29697

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