Regulation of HMG-CoA reductase in MCF-7 cells by genistein, EPA, and DHA, alone and in combination with mevastatin.
We investigated the regulation of HMG-CoA reductase in MCF-7 human breast cancer cells by genistein, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). All three compounds down-regulated reductase activity, primarily through post-transcriptional effects. In mevastatin-treated cells, only genistein and DHA abrogated the induction of reductase activity caused by this competitive inhibitor. Diets rich in soy isoflavones and fish oils, therefore, may exert anti-cancer effects through the inhibition of mevalonate synthesis in the breast. Genistein and DHA, in particular, may augment the efficacy of statins, increasing the potential for use of these drugs in adjuvant therapy for breast cancer.
Duncan
Robin E
RE
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, FitzGerald Building, 150 College Street, Toronto, Ont., Canada M5S 3E2.
El-Sohemy
Ahmed
A
Archer
Michael C
MC
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D004032:Diet; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000187:drug effects* / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D000924:Anticholesteremic Agents; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D019833:Genistein; D006903:Hydroxymethylglutaryl CoA Reductases