Phytosterols inhibit the tumor growth and lipoprotein oxidizability induced by a high-fat diet in mice with inherited breast cancer

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Phytosterols inhibit the tumor growth and lipoprotein oxidizability induced by a high-fat diet in mice with inherited breast cancer

Received 19 August 2011; received in revised form 2 January 2012; accepted 17 January 2012. published online 04 June 2012.
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Abstract 

Dietary phytosterol supplements are readily available to consumers since they effectively reduce plasma low-density lipoprotein cholesterol. Several studies on cell cultures and xenograft mouse models suggest that dietary phytosterols may also exert protective effects against common cancers. We examined the effects of a dietary phytosterol supplement on tumor onset and progression using the well-characterized mouse mammary tumor virus polyoma virus middle T antigen transgenic mouse model of inherited breast cancer. Both the development of mammary hyperplastic lesions (at age 4 weeks) and total tumor burden (at age 13 weeks) were reduced after dietary phytosterol supplementation in female mice fed a high-fat, high-cholesterol diet. A blind, detailed histopathologic examination of the mammary glands (at age 8 weeks) also revealed the presence of less-advanced lesions in phytosterol-fed mice. This protective effect was not observed when the mice were fed a low-fat, low-cholesterol diet. Phytosterol supplementation was effective in preventing lipoprotein oxidation in mice fed the high-fat diet, a property that may explain — at least in part — their anticancer effects since lipoprotein oxidation/inflammation has been shown to be critical for tumor growth. In summary, our study provides preclinical proof of the concept that dietary phytosterols could prevent the tumor growth associated with fat-rich diet consumption.

Abbreviations: Abc, ATP-binding cassette transporter, Fasn, fatty acid synthase, GDI, GDP dissociation inhibitor, GP, generalized polarization, HDL, high-density lipoprotein, HFHC, high-fat, high-cholesterol, Hmgcr, 3-hydroxy-3-methyl-glutaryl-CoA reductase, LDL, low-density lipoprotein, Ldlr, LDL receptor, LFLC, low fat, low cholesterol, LXR, liver X receptor, MMTV, mouse mammary tumor virus, oxLDL, oxidized LDL, PAF-AH, platelet-activated factor acetyl-hydrolase, PON1, arylesterase or paraoxonase, PyMT, polyoma virus middle T antigen, REM, relative electrophoretic mobility, Scarb1 (or SR-BI), scavenger receptor class B type I, Srebf, sterol response element binding protein, Tg, transgenic

Keywords: Phytosterols, Breast cancer, Cholesterol, Lipoprotein, Oxidation, MMTV-PyMT mice