School of Public Health and Health Professions at the University at Buffal investigated the effects of beta-sitosterol and tamoxifen on the cultured breast cancer cells. The study led by Awad concluded that "these results suggest that the combination regimen of dietary beta-sitosterol and tamoxifen chemotherapy may be beneficial in the management of breast cancer patients"[1]. Tamoxifen is drug used for the treatment of breast cancer and works as a selective estrogen receptor modulator. Therefore it only works on estrogen receptor positive breast cancer cells. They tested the effect of beta-sitosterol and tamoxifen, separately and combined, on the growth of estrogen receptor positive breast cancer cells and estrogen receptor negative breast cancer cells. They found that a treatment with beta-sitosterol inhibited the growth of both type of cells whereas tamoxifen only inhibited of estrogen receptor positive breast cancer cells. A combined treatment further inhibited the growth of both cell types. Both beta-sitosterol and tamoxifen modulated the ceramide metabolism. Ceramides act as a signaling molecule, regulating differentiation, proliferation, programmed cell death and apoptosis. Beta-sitosterol increased ceramide levels by stimulating ceramide production whereas tamoxifen tamoxifen increased ceramide levels by inhibting ceramide glycosylation.
A study conducted by the State University of New York concluded that beta-sitosterol is an effective apoptosis-promoting phytochemical and more dietary phytosterols may protect against breast cancer. The scientists studied the effect of beta-sitosterol on cultured breast cancer cells and adenocarcinoma cells. Beta-sitosterol concentrated in the cell membranes and significantly inhibited tumor cell growth. It increased the Fas levels and caspase-8 activity [2]. Beta-sitosterol seems to induce apoptosis of cancer cells through two pathways: the extrinsic and intrinsic pathways, which are catalyzed by by the initiator caspases 8 and 9 respectively. Both pathways result in the activation of caspase 3, which is an effector caspases that cleaves protein substrates within the cell resulting in the apoptotic process. Awad and his team found that beta-sitosterol treatment of cultured breast cancer cells increased the activities of caspases 8 and 9 by 39% and 80% respectively, resulting in a a three-fold increase in the activity of caspase 3 [3].
In another in-vivo experiment conducted by Awad also showed that beta-sitosterol inhibited the growth of breast cancer cells by up to 80%, caused a six-fold increase in apoptosis cells but showed no cytotoxicity. The found no effect of beta-sitosterol on the level of protein phosphatase 2A in the tumor cells [4].
A study by Ju et al investigated the estrogenic effects of the plant sterols beta-sitosterol, beta-sitosterol glucoside and Moducare (mixture of beta-sitosterol, beta-sitosterol glucoside). The test was carried out on estrogen dependent human breast cancer cells in vitro and in vivo. The researchers concluded that beta-sitosterol and Moducare stimulated cancer cells in vitro and that dietary beta-sitosterol and Moducare protected against estrogen stimulated tumor growth. These findings suggest that beta-sitosterol could have potential benefits for women with a risk for estrogen-dependent breast cancer [5].
[1] Awad AB, Barta SL, Fink CS, Bradford PG. " beta-Sitosterol enhances tamoxifen effectiveness on breast cancer cells by affecting ceramide metabolism."Mol Nutr Food Res. 2008 Apr;52(4):419-26.
[2] Awad AB, Chinnam M, Fink CS, Bradford PG. " beta-Sitosterol activates Fas signaling in human breast cancer cells." Phytomedicine. 2007 Nov;14(11):747-54.
[3] Awad AB, Roy R, Fink CS. "Beta-sitosterol, a plant sterol, induces apoptosis and activates key caspases in MDA-MB-231 human breast cancer cells. "Oncol Rep. 2003 Mar-Apr;10(2):497-500
[4] Awad AB, Downie AC, Fink CS. "Inhibition of growth and stimulation of apoptosis by beta-sitosterol treatment of MDA-MB-231 human breast cancer cells in culture." Int J Mol Med. 2000 May;5(5):541-5.
[5] Ju YH, Clausen LM, Allred KF, Almada AL, Helferich WG. "Beta-sitosterol, beta-sitosterol glucoside, and a mixture of beta-sitosterol and beta-sitosterol glucoside modulate the growth of estrogen-responsive breast cancer cells in vitro and in ovariectomized athymic mice." J. Nutr. 134: 1145-1151.
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