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Phytosterols are plant sterols that are similar in structure to cholesterol and exist in several forms in plants including sitosterol, which is the most abundant phytosterol. Rich sources of phytosterols include grain legumes, cereal grains, vegetable oils and nuts. It has been discerned from previous studies that phytosterols may be useful in prevention of both cardiovascular disease and cancer due to the possibility that phytosterols may inhibit the production of carcinogens, cancer-cell growth, invasion and metastasis, and promote apoptosis of cancerous cells. The purpose of the paper by Woyengo et al. (2009) was to review and analyse the results of recent studies on the relationship between phytosterol consumption and cancer risk and the possible mechanisms involved.
Cancer is a group of diseases caused by the uncontrolled growth of cells that spread from the original manifestation sites to other parts of the body. They occur when the genes controlling cell growth and apoptosis (controlled cell death) are damaged, resulting in altered production and/or activity of the proteins they encode.
It was found that â-sitosterol increased the activities of the antioxidant enzymes, superoxide dismutase and glutathione peroxidise in vivo, indicating that phytosterols can protect cells from damage by reactive oxygen species. Furthermore, phytosterols have been proved to promote apoptosis which is an important mechanism in the inhibition of carcinogenesis. The mechanisms by which â-sitosterol promotes apoptosis includes increased activity of caspase-3 (an enzyme involved in cell apoptosis) as well as pro-apoptotic enzymes (ERK and p38) and reduced activity of anti-apoptotic enzymes (Pl3 and AKT), all resulting in apoptosis of the cancerous cell. The alteration in caspase-3 activity after â-sitosterol administration was suggested to be due to the alteration of structure and function of cancer cell membranes as a result of the incorporation of the phytosterol into the cell membrane and consequently disruption of signal transduction and cellular phosphorylation cascades.
High intake and elevated blood concentrations of cholesterol are associated with cancer which may be due to the consequential increased survival and reduced apoptosis of cells as the increased levels of cholesterol accumulate in the cell membranes. The increased apoptosis observed with reduced cholesterol levels was suggested to be attributable to the increased activity of caspase-3 and reduced Akt and ERK activity due to the absence of cholesterol in the lipid rafts of the cell membrane.
To conclude, phytosterols do appear to inhibit the development of various cancers by inhibiting growth and promoting apoptosis of cancer cells by the activation of caspase enzymes which results from the incorporation of phytosterols into the cell membrane. This in turn leads to an increase in activity of enzymes involved in extra- and intracellular signal-transduction pathways that activate the caspase enzymes. Phytosterols could also inhibit cancer development by lowering blood cholesterol, since high blood cholesterol, and thus high cholesterol levels in the lipid rafts of cell membranes, are associated with reduced apoptosis of cancer cells. This combined evidence supports the anti-carcinogenic action of phytosterols and highlights the importance of their dietary inclusion in the prevention and treatment of cancer. (Woyengo et al. European Journal of Clinical Nutrition (2009) 63: 813–820; doi:10.1038/ejcn.2009.29; 03/06/09).
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