beta-Sitosterol activates Fas signaling in human breast cancer cells.
beta-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. beta-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 beta-sitosterol 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 beta-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 beta-sitosterol is an effective apoptosis-promoting agent and that incorporation of more phytosterols in the diet may serve a preventive measure for breast cancer.
Awad
A B
AB
Department of Exercise and Nutrition Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA. awad@buffalo.edu
Chinnam
M
M
Fink
C S
CS
Bradford
P G
PG
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D053222:Fas Ligand Protein / Q000378:metabolism*; D005260:Female; D006801:Humans; D008517:Phytotherapy; D010946:Plants, Medicinal; D015398:Signal Transduction / Q000187:drug effects; D012855:Sitosterols / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000972:Antineoplastic Agents, Phytogenic; D053222:Fas Ligand Protein; D012855:Sitosterols; C025473:gamma-sitosterol