olive oil good for Her2+ [I think]
olive oil good for Her2+ [I think] Brain not working today- see what you think, dilly
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
J. A. Menendez 1*, L. Vellon 2, R. Colomer 3, and R. Lupu 1*
1 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
2 Department of Medicine, Breast Cancer Translational Research Laboratory, Evanston Northwestern Healthcare Research Institute, Evanston, IL, USA
3 Institut Catala d’Oncologia, Hospital Universitari de Girona Dr Josep Trueta, Girona, Spain
* To whom correspondence should be addressed.
J. A. Menendez, E-mail: jmenendez-at-enh.org
R. Lupu, E-mail: r-lupu-at-northwestern.edu
Abstract
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 (HerceptinTM), a humanized monoclonal antibody binding with high affinity to the ectodomain of the Her-2/neu-coded p185Her-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 p185Her-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 µg/ml trastuzumab). Remarkably, the concurrent exposure to OA and suboptimal concentrations of trastuzumab (5 µg/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 p27Kip1, 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.
Keywords: apoptosis; breast cancer; fatty acids; Her-2/neu; oleic acid; trastuzumab.
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Looks too short for a full report. Dilly,
To be honest, there is insufficient information here to form a judgement whether or not they were giving good evidence of a correlation between consuming olive oil and better survival for those who are HER2 positive.
I’d want to know how they put together the test arms (age distribution, stages, progress of the disease, medication being received, any other health problems, the numbers involved etc) to check for a fair comparison. Also, was this sponsored by anyone marketing olive oil?
Is its effect neutral for those of us who are HER2 negative?
However, olive oil tastes better than most other vegetable oils so I use iy all the time for cooking, salad dressings etc. Nobody has said it is bad for us unless we overconsume as with any fat. So, if you want to give it a go, why not?
Holey.
It’s a cell study This study relates to the effect of various oils on cells in the laboratory, not in lab animals or people, so it is very tentative.
However, there are some indicators that it might be worth a try. A study at ASCO found that Italian her2+++ women actually do much better than her2— women if they have anthracyclines and taxanes (and this was without herceptin, since this was a retrospective study). I don’t know of any other situation where her2+++ have done better. One of the roles of olive oil on her2+++ cells seems to be chemosensitizing, so this may explain it. There also was a study in which women who were given flaxseed muffins had the level of her2 in their cancers drop and flaxseed is rich in two possibly beneficial fatty acids: olive oil (the best common fatty acid for her2+++ in Menendez’s ) and alphalinolenic acid (the second best common ). Menendez’s work also indicated that omega-6 might be bad for her2+++ breast cancers.
In any event, according to a recent Food Programme on the radio, olive oil is healthiest for cooking anyway, while oils containing alphalinolenic acid may be beneficial uncooked, so you are unlikely to be hurting yourself by switching over to olive oil.
Thanks Christine! I read it too quickly and didn’t notice it was an experiment on cells rather than people.
All successful drugs begin in the lab. Dr Menedez is reported to have said that it is quite easy to attain the blood levels of oleic acid required by eating (drinking?) the oil. All drugs begin by someone observing an effect or making a deduction based on other observation. Then there is work in the culture dish. Then there is work to try and make a drug from which enormous profits will be derived. Why not side step the profit bit. We can afford the olive oli but I bet the NHS could not afford a drug based on it! Apart from the fact that we will be solemnly assured by pharma that it will take years to develop and test.
Do we have years?
Overall it makes sense because of the Italian connection, so what have you got to lose by trying it? The same author found that GLA from primrose oil or Starflower oil is more effective. I take 6 capsules of starflower oil a day and it relieves the discomfort in my right breast so I am quite happy to take it and see what happens. There is precious little enough for for us HER2 positive types.
I did ask our local cancer hospital if they would do research into this and provided them with the references but got a whole load of guff in return. (Apparently I don’t understand breast cancer!)
I would suggest that I understand it enough to know that promising areas of research are ignored and unfunded because hospitals and the staff are tied into the pharmacological and chemical model as pushed by the drug companies. Perhaps it is time for cancer patients to demand a little more imagination and independance from people like the Wellcome Foundation and even CRUK. They could start by looking at DiChloroAcetate, which is used for rare metabolic disorders and has few known side-effects. Anyone read the New Scientist on that subject? A whole new approach to cancer by returning mitochondria to their proper energy-creating function. There’s a petition on the Downing Street Webisite if you want to add your voice to it, and I will be raising the matter at our local patient’s group later this week.
Meantime, good luck with this and do let us know if you get any good effect.