Breast cancer and impact nutrition and nutrients: Olive oil doubles effect of Herceptin in breast cancer and protects against recurrence of breast cancer.
14 January 2005: source: Pubmed and MedinieuwsSuccessively a Dutch press release and official study publication from Pubmed assembled behind.
The frequent use of olive oil in the Mediterranean diet seems breast cancer. protection against Scientists at Northwestern University Feinberg School for Medicine in Chicago found molecular evidence for the effect of oleic acid and published this in the Annals of Oncology.
Olive oil is rich in oleic acid. In laboratory experiments with borstkankercel lines discovered the American researchers that oleic acid in important degree the overexpression of the Her-2/neu oncogene. suppressed This overactivity of oncogene is at more than one fifth of the breast cancer patients associated with a very aggressive tumor with a poor prognosis.
In other tests showed the researchers that oleic acid also trastuzumab (Herceptin) effect of strengthened. Trastuzumab is a monoclonal antibody that blocks the Her-2/neu oncogene-. If third proof reports project leader Javier Menendez that oleic acid increases the expression of a tumorsuppressoreiwit that plays a role in the development of resistance to treatment with trastuzumab.
According to Menendez support his study results epidemiological research where it is demonstrated that the Mediterranean diet offers protection against cancer, among others.He sees for the future role of oleic acid in the treatment of cancer. Possible can a diet based on oleic acid resistance to trastuzumab prevent or retard.
Ann Oncol. 2005 Jan 10; [Epub ahead of print]
Oleic acid, the main fatty acid or monounsaturated fats, olive oil suppresses Her-2/neu (erbB-2) expression and synergistically enhances the growth inhibitory effects of trastuzumab (HerceptinTM) in breast cancer cells with Her-2/neu oncogene amplification.
Menendez YES, L, R, R Vellon Colomer Lupu.
Department of Medicine, Breast Cancer Translational Research Laboratory, Evanston Northwestern Healthcare Research Institute, Evanston, IL, USA; Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
BACKGROUND: The relationship between the intake of olive oil, the richest dietary source of monounsaturated fats the fatty acid oleic acid (OA; 18: 1n-9), and breast cancer risk and progression has become a controversial issue. Moreover, it has been suggested that the protective effects of olive oil against breast cancer may be due to some other components of the oil rather than to a direct effect or OA.
METHODS: Using flow cytometry, western blotting, immunofluorescence microscopy, metabolic status (MTT), soft-agar colony formation, enzymatic in situ labeling orapoptosis-induced DNA double-Beach breaks (TUNEL assay analysis), and caspase-3-dependent poly-ADP ribose polymerase (PARP) cleavage assays, we characterized the effects of exogenous supplementation with OA on the expression of Her-2/neu oncogene, which plays an active role in breast cancer etiology and progression. In addition, we investigated the effects of OA on the efficacy of trastuzumab (Herceptin (TM)), a humanized monoclonal antibody binding with high affinity to the ectodomain of the Her-2/neu-coded p185 (Her-2/neu) oncoprotein. To study these issues we used BT-474 and SKBr-3 breast cancer cells, which naturally exhibit amplification of the Her-2/neu oncogene.
RESULTS: Flow cytometric analyses demonstrated a dramatic (up to 46%) reduction or cell surface-associated p185 (Her-2/neu) following treatment of the Her-2/neu-overexpressors BT-474 and SK-Br3 with OA. Indeed, this effect was comparable to that found following exposure to optimal concentrations or trastuzumab (up to 48% reduction with 20 microg/ml trastuzumab). Remarkably, the competitor exposure to OA and suboptimal concentrations or trastuzumab (5 microg/ml) synergistically down-regulated Her-2/neu expression, as determined by flow cytometry (up to 70% reduction), immuno-blotting, immunofluorescence and microscopy studies. The nature of the interaction between OA and trastuzumab revealed a strong cytotoxic synergism, as assessed by MTT-based cell viability and anchorage-independent soft-agar colony formation assays. Moreover, OA co-exposure synergistically enhanced trastuzumab efficacy towards Her-2/neu overexpressors by promoting DNA fragmentation associated with apoptotic cell death, as confirmed by TUNEL and caspase-3-dependent cleavage PARP. In addition, treatment with OA and trastuzumab dramatically increased both the expression and the nuclear accumulation or p27, cyclin-dependent kinase (Kip1) a inhibitor playing a key role in the onset and progression of Her-2/neu-related breast cancer. Finally, OA co-exposure significantly enhanced the ability of trastuzumab to inhibit signaling pathways downstream of Her-2/neu, including phosphoproteins such as AKT and MAPK.
CONCLUSIONS: These findings demonstrate that OA, the main fatty acid or monounsaturated fats, olive oil suppresses Her-2/neu overexpression, which, in turn, interacts synergistically with anti-Her-2/neu immunotherapie by promoting apoptotic cell death of breast cancer cells with Her-2/neu oncogene amplification. This previously unrecognized property or OA offers a novel molecular mechanism by which individual fatty acids may regulate the malignant behavior of breast cancer cells and therefore be helpful in the design of future epidemiological studies and, eventually, dietary counseling.
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