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Anticancer effects of beta-sitosterol

Beta-sitosterol is mainly studied for its cholesterol-lowering properties but many studies also find that the phytochemical may help to prevent cancer. Epidemiological and experimental studies have suggested a protective role of beta-sitosterol in the development of some types of cancer such as breast, colon and prostate cancer. In-vivo studies have shown that the phytochemical inhibited proliferation and induce apoptosis in human solid tumors such as colon and breast cancers.

A Japanese study led by Imanaka demonstrated that the oral intake of beta-sitosterol, encapsulated in a liposome, was able to prevent tumour metastasis in rats, although the phytochemical was not absorbed in the serum. The researchers believed that beta-sitosterol works by stimulating the gut immune surveillance systems, as indicated by an increase in natural killer cell activity and production of immune response cytokines [1]. Park and co-workers concluded in their study that "beta-sitosterol potently induces apoptosis in U937 cells (these are leukemia cells) and that beta-sitosterol-induced apoptosis is related to the selective activation of caspase-3 and induction of Bax/Bcl-2 ratio." Beta-sitosterol induced apoptosis in the leukemia cells in a dose-dependent manner [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. Korean study lead by Moon also found this effect of beta-sitosterol on caspase activation on cultured fibrosarcoma cells: treatment of the cells with an caspase-3 inhibitor inhibited the beta-sitosterol induced apoptosis. Treatment of the fibrosarcoma cells with beta-sitosterol also induced activation (phosphorylation) of extracellular-signal regulating kinase and blocked protein kinase B, which inhibits apoptotic processes [3]. Nakamura and co-workers found that beta-sitosterol restored the impaired gap junctional intercellular communication of transfected rat liver epithelial cells. The beta-sitosterol used in this experiment was extracted from the husks of psyllium seeds. Beta-sitosterol and also stigmasterol increased the level of gap junction proteins and restored their level of phosphorylation to levels similar to nontransfected cells [4].

Epidemiological evidence has shown that men consuming high amounts of plant products have a lower risk of prostate cancer. Von Holtz and colleagues investigated the possible effect of the plant sterol, beta-sitosterol, on cancer cells. They found that beta-sitosterol decreased the numbers of prostate cancer cells and increased apoptosis. Beta-sitosterol the production of ceramide, which is cellular signaling molecule regulating the differentiation, proliferation, programmed cell death and apoptosis of cells [5]. An in-vitro experiment with bone marrow cells showed that beta-sitosterol reduced the genotoxic damage caused by doxorubicin [6]. Beta-sitosterol significantly reduced the frequency of sister chromatid exchanges, which are exchange of genetic material between two identical sister chromatids. When the frequency of chromatid exchange is too high, cell damage can occur.

[1] Imanaka H, Koide H, Shimizu K, Asai T, Kinouchi Shimizu N, Ishikado A, Makino T, Oku N. " Chemoprevention of tumor metastasis by liposomal beta-sitosterol intake" Biol Pharm Bull. 2008 Mar;31(3):400-4.
[2] Park C, Moon DO, Rhu CH, Choi BT, Lee WH, Kim GY, Choi YH. " Beta-sitosterol induces anti-proliferation and apoptosis in human leukemia U937 cells through activation of caspase-3 and induction of Bax/Bcl-2 ratio." Biol Pharm Bull. 2007 Jul;30(7):1317-23.
[3] Moon DO, Lee KJ, Choi YH, Kim GY. "Beta-sitosterol-induced-apoptosis is mediated by the activation of ERK and the downregulation of Akt in MCA-102 murine fibrosarcoma cells." Int Immunopharmacol. 2007 Aug;7(8):1044-53.
[4] .Nakamura Y, Yoshikawa N, Hiroki I, Sato K, Ohtsuki K, Chang CC, Upham BL, Trosko JE. "Beta-sitosterol from psyllium seed husk (Plantago ovata Forsk) restores gap junctional intercellular communication in Ha-ras transfected rat liver cells." Nutr Cancer. 2005;51(2):218-25.
[5]Von Holtz RL, Fink CS, Awad AB. " beta-Sitosterol activates the sphingomyelin cycle and induces apoptosis in LNCaP human prostate cancer cells." Nutr Cancer. 1998;32(1):8-12.
[6] Paniagua-Pérez R, Madrigal-Bujaidar E, Reyes-Cadena S, Alvarez-González I, Sánchez-Chapul L, Pérez-Gallaga J, Hernández N, Flores-Mondragón G, Velasco O. " Cell protection induced by beta-sitosterol: inhibition of genotoxic damage, stimulation of lymphocyte production, and determination of its antioxidant capacity. " Arch Toxicol. 2008 Feb 6.

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