7 alpha-Hydroxy-beta-Sitosterol from Chisocheton tomentosus Induces Apoptosis via Dysregulation of Cellular Bax/Bcl-2 Ratio and Cell Cycle Arrest by Downregulating ERK1/2 Activation

Tasyriq, Mohammad and Najmuldeen, Ibrahim A. and In, Lionel L.A. and Mohamad, Khalit and Awang, Khalijah and Nagoor, Noor Hasima (2012) 7 alpha-Hydroxy-beta-Sitosterol from Chisocheton tomentosus Induces Apoptosis via Dysregulation of Cellular Bax/Bcl-2 Ratio and Cell Cycle Arrest by Downregulating ERK1/2 Activation. Evidence-Based Complementary and Alternative Medicine, 2012. p. 765316. ISSN 1741-427X, DOI https://doi.org/10.1155/2012/765316.

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Abstract

In continuation of our interest towards the elucidation of apoptotic pathways of cytotoxic phytocompounds, we have embarked upon a study on the anticancer effects of 7 alpha-hydroxy-beta-sitosterol (CT1), a rare natural phytosterol oxide isolated from Chisocheton tomentosus. CT1 was found to be cytotoxic on three different human tumor cell lines with minimal effects on normal cell controls, where cell viability levels were maintained >= 80 upon treatment. Our results showed that cell death in MCF-7 breast tumor cells was achieved through the induction of apoptosis via downregulation of the ERK1/2 signaling pathway. CT1 was also found to increase proapoptotic Bax protein levels, while decreasing anti-apoptotic Bcl-2 protein levels, suggesting the involvement of the intrinsic pathway. Reduced levels of initiator procaspase-9 and executioner procaspase-3 were also observed following CT1 exposure, confirming the involvement of cytochrome c-mediated apoptosis via the mitochondrial pathway. These results demonstrated the cytotoxic and apoptotic ability of 7 alpha-hydroxy-beta-sitosterol and suggest its potential anti-cancer use particularly on breast adenocarcinoma cells.

Item Type:	Article
Funders:	UNSPECIFIED
Uncontrolled Keywords:	Breast-Cancer Cells, Beta-Sitosterol, In-Vitro, Phytosterols, 7-Beta-Hydroxycholesterol, 7-Beta-Hydroxysitosterol, Derivatives, Limonoids, Meliaceae, Sterols
Subjects:	Q Science > QH Natural history > QH301 Biology
Divisions:	Faculty of Science > Institute of Biological Sciences
Depositing User:	miss munirah saadom
Date Deposited:	15 Jul 2013 23:38
Last Modified:	29 Jan 2020 06:22
URI:	http://eprints.um.edu.my/id/eprint/7783

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