14 januari 2005: Bron: Pubmed en Medinieuws

Achtereenvolgens een Nederlands persbericht en officiële studiepublicatie uit Pubmed achter elkaar gezet.

Het veelvuldige gebruik van olijfolie in het Mediterraan dieet lijkt bescherming te bieden tegen borstkanker. Wetenschappers van de Northwestern University Feinberg School for Medicine in Chicago vonden moleculair bewijs voor het effect van oliezuur en publiceerden dit in de Annals of Oncology.

Olijfolie is rijk aan oliezuur. In laboratoriumexperimenten met borstkankercellijnen ontdekten de Amerikaanse onderzoekers dat oliezuur in belangrijke mate de overexpressie van het oncogen Her-2/neu onderdrukt. Overactiviteit van dit oncogen is bij meer dan eenvijfde van de borstkankerpatiënten geassocieerd met een zeer agressieve tumor met een slechte prognose.
In andere testen toonden de onderzoekers aan dat oliezuur tevens het effect van trastuzumab (Herceptin) versterkt. Trastuzumab is een monoklonale antistof die het Her-2/neu-oncogen blokkeert. Als derde bewijs meldt onderzoeksleider Javier Menendez dat oliezuur de expressie verhoogt van een tumorsuppressoreiwit dat een rol speelt in de ontwikkeling van resistentie tegen behandeling met trastuzumab.
Volgens Menendez ondersteunen zijn studieresultaten epidemiologisch onderzoek waarin is aangetoond dat het Mediterrane dieet bescherming biedt tegen onder meer kanker.Hij ziet voor de toekomst een rol weggelegd voor oliezuur in de behandeling van kanker. Mogelijk kan een dieet gebaseerd op oliezuur resistentie tegen trastuzumab voorkomen of vertragen.

Ann Oncol. 2005 Jan 10; [Epub ahead of print]

Oleic acid, the main monounsaturated fatty acid of 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 JA, Vellon L, Colomer R, Lupu R.

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 the monounsaturated 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 of OA.

METHODS: Using flow cytometry, western blotting, immunofluorescence microscopy, metabolic status (MTT), soft-agar colony formation, enzymatic in situ labeling of apoptosis-induced DNA double-strand breaks (TUNEL assay analyses), 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 of 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 of trastuzumab (up to 48% reduction with 20 microg/ml trastuzumab). Remarkably, the concurrent exposure to OA and suboptimal concentrations of trastuzumab (5 microg/ml) synergistically down-regulated Her-2/neu expression, as determined by flow cytometry (up to 70% reduction), immunoblotting, and immunofluorescence microscopy studies. The nature of the cytotoxic interaction between OA and trastuzumab revealed a strong 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 PARP cleavage. In addition, treatment with OA and trastuzumab dramatically increased both the expression and the nuclear accumulation of p27(Kip1), a cyclin-dependent kinase 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 monounsaturated fatty acid of olive oil, suppresses Her-2/neu overexpression, which, in turn, interacts synergistically with anti-Her-2/neu immunotherapy by promoting apoptotic cell death of breast cancer cells with Her-2/neu oncogene amplification. This previously unrecognized property of 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.
,br> PMID: 15642702 [PubMed - as supplied by publisher]

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