b-Sitosterol activates Fas signaling in human breast cancer cells

b-Sitosterol is the most abundant phytosterol. Phytosterols are enriched in legumes, oil seeds and unrefined plant oils as found in foods such as peanut butter, pistachios and sunflower seeds. b-Sitosterol inhibits the growth of several specific types of tumor cells in vitro and decreases the size and the extent of tumor metastases in vivo. The effects of bsitosterol on the extrinsic apoptotic programmed cell death pathway in human breast MCF-7 and MDA-MB-231 adenocarcinoma cells were examined, along with the extent of its incorporation into cellular membranes and its effects on cell growth, expression of Fas receptor pathway proteins, and caspase-8 activity. The results show that b-sitosterol exposure promotes its enrichment in transformed cell membranes and significantly inhibits tumor cell growth. Concurrently, Fas levels and caspase-8 activity are significantly increased. These actions are specific, as expression of other proteins of the Fas receptor pathway, including Fas ligand, FADD, p-FADD and caspase-8, remain unchanged. These findings support the hypothesis that b-sitosterol is an effective apoptosis-promoting agent and that incorporation of more phytosterols in the diet may serve a preventive measure for breast cancer. r 2007 Elsevier GmbH. All rights reserved.