Mediterranean diet, olive oil and cancer.
Olive oil is an integral ingredient of the "Mediterranean diet" and accumulating evidence suggests that it may have a potential role in lowering the risk of several types of cancers. The mechanisms by which the cancer-preventing effects of olive oil can be performed, however, are not known. We recently hypothesized that a novel molecular explanation concerning the anti-cancer actions of olive oil may relate to the ability of its monounsaturated fatty acid (MUFA) oleic acid (OA; 18:1n-9) to specifically regulate cancer-related oncogenes. Supporting our hypothesis, exogenous supplementation of cultured breast cancer cells with physiological concentrations of OA was found to suppress the overexpression of HER2 (Her-2/neu, erbB-2), a well-characterized oncogene playing a key role in the etiology, progression and response to chemotherapy and endocrine therapy in approximately 20% of breast carcinomas. OA treatment was also found to synergistically enhance the efficacy of trastuzumab, a humanized monoclonal antibody binding with high affinity to the ectodomain (ECD) of the Her2-coded p185(HER2) oncoprotein. Moreover, OA exposure significantly diminished the proteolytic cleavage of the ECD of HER2 and, consequently, its activation status, a crucial molecular event that determines both the aggressive behavior and the response to trastuzumab of Her2-overexpressing breast carcinomas. Our most recent findings further reveal that OA exposure may suppresses HER2 at the transcriptional level by up-regulating the expression of the Ets protein PEA3 -a DNA-binding protein that specifically blocks HER2 promoter activity- in breast, ovarian and stomach cancer cell lines. This anti-HER2 property of OA offers a previously unrecognized molecular mechanism by which olive oil may regulate the malignant behavior of cancer cells. From a clinical perspective, it could provide an effective means of influencing the outcome of Her-2/neu-overexpressing human carcinomas with poor prognosis. Indeed, OA-induced transcriptional repression of HER2 oncogene may represent a novel genomic explanation linking "Mediterranean diet", olive oil and cancer as it seems to equally operate in various types of Her-2/neu-related carcinomas.
Colomer
Ramón
R
Medical Oncology, Institut Catala d'Oncologia, Hospital de Girona Dr. Josep Trueta, Girona, Spain. rcolomer@ico.scs.es
Menéndez
Javier A
JA
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics / Q000517:prevention & control; D045744:Cell Line, Tumor / Q000187:drug effects / Q000201:enzymology; D002648:Child; D004032:Diet; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology / Q000627:therapeutic use*; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D018734:Genes, erbB-2 / Q000187:drug effects; D006801:Humans; D006946:Hyperinsulinism / Q000150:complications; D008297:Male; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000453:epidemiology / Q000517:prevention & control*; D009765:Obesity / Q000150:complications / Q000453:epidemiology; D019301:Oleic Acid / Q000494:pharmacology / Q000627:therapeutic use; D000069463:Olive Oil; D010938:Plant Oils / Q000494:pharmacology / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004042:Dietary Fats, Unsaturated; D019301:Oleic Acid; D000069463:Olive Oil; D010938:Plant Oils; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab