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Does Cholesterol Feed Prostate Cancer?
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Zhuang L, Kim J, Adam RM, Solomon KR, Freeman MR. Cholesterol targeting alters lipid raft composition and cell survival in prostate cancer cells and xenografts. J Clin Invest. 2005 Mar 17; [Epub ahead of print] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15776112 The Urological Diseases Research Center, Department of Urology, Children's Hospital Boston, Boston, Massachusetts, USA. ABSTRACT (Translation below) Lipid rafts are cholesterol- and sphingolipid-enriched microdomains in cell membranes that regulate phosphorylation cascades originating from membrane-bound proteins. In this study, we tested whether alteration of the cholesterol content of lipid rafts in prostate cancer (PCa) cell membranes affects cell survival mechanisms in vitro and in vivo. Simvastatin, a cholesterol synthesis inhibitor, lowered raft cholesterol content, inhibited Akt1 serine-threonine kinase (protein kinase Balpha)/protein kinase B (Akt/PKB) pathway signaling, and induced apoptosis in caveolin- and PTEN-negative LNCaP PCa cells. Replenishing cell membranes with cholesterol reversed these inhibitory and apoptotic effects. Cholesterol also potentiated Akt activation in normal prostate epithelial cells, which were resistant to the apoptotic effects of simvastatin. Elevation of circulating cholesterol in SCID mice increased the cholesterol content and the extent of protein tyrosine phosphorylation in lipid rafts isolated from LNCaP/sHB xenograft tumors. Cholesterol elevation also promoted tumor growth, increased phosphorylation of Akt, and reduced apoptosis in the xenografts. Our results implicate membrane cholesterol in Akt signaling in both normal and malignant cells and provide evidence that PCa cells can become dependent on a cholesterol-regulated Akt pathway for cell survival. Mice experiments The Boston team injected human prostate cancer cells into mice and watched them grow. When the animals were fed high cholesterol diets, cholesterol was found to accumulate in the outer membranes of tumour cells. This appeared to alter chemical signalling patterns within the cells. As a result, they resisted signals telling them to commit suicide and instead continued to proliferate in the uncontrolled fashion seen in cancer. The increased cholesterol levels did not trigger new cancers in the mice. But six weeks after the tumour cells were injected, mice on the high-cholesterol diets had twice as many tumours as animals on ordinary diets. Their tumours were also much larger in size. When the cells were exposed to the cholesterol-lowering drug simvastatin, cell death increased and tumours stopped proliferating. But replenishing cell membranes with cholesterol caused the cancer to run out of control again. The study was reported by the BBC, thus: Cholesterol feeds prostate cancerhttp://news.bbc.co.uk/2/hi/health/4359117.stmProstate cancer can be a killer A team from Boston's Children Hospital found that cholesterol-lowering statin drugs may inhibit prostate cancer growth. The findings may help explain why prostate cancer is more common in the West, where diets tend to be high in cholesterol. Rates of prostate cancer in rural parts of China and Japan, where low fat diets are the norm, are up to 90% less than in the West. Yet when Eastern men migrate to the West their chances of being diagnosed with prostate cancer increase. This has led doctors to suspect that environmental factors – such as diet – may play a significant role in the development of the disease. (COMMENT: That's been known for over a century. BG) Lead researcher Dr Michael Freeman said: "Our study opens up a new paradigm in thinking about how cancer might be controlled pharmacologically by manipulating cholesterol. . . . Our data support the notion that cholesterol-lowering drugs – which are widely used and fairly safe – might be effective in prevention of prostate cancer, or as an adjunctive therapy." (COMMENT: Note the expression 'fairly safe'. Shading the truth? BG) Chris Hiley, of the UK Prostate Cancer Charity, said: "This research is clearly at an early stage, as it was accomplished in mouse cells, not men, but it's heartening to see a plausible connection made between processes inside cells and the Westernised high fat diet that seem to increase the risk of prostate cancer occurring. "The results do open up thinking about new drug therapies. But there is also a low tech option any man could attempt today. Adopt a healthy low cholesterol diet and active lifestyle. Cut down on saturated fats, reduce the total amount of fat eaten but eat oily fish, and eat a high fibre diet – with porridge oats, and plenty of fresh fruit and vegetables." |
COMMENT:
Studies like this are really quite meaningless — taking just one aspect of some peoples' diet and attributing rates of cancer to it, without looking at the whole package.
The article stated that "Rates of prostate cancer in rural parts of China and Japan, where low fat diets are the norm, are up to 90% less than in the West."
But rates of prostate cancer amongst the Inuit eating their traditional diet, which contained more than 80% calories from fat, were zero. In fact ALL rates of cancer were zero![1-4]
I don't place much store in experiments on mice, frankly, as their response to nutrition is quite different from a human's. What matters is what happens in the real world. There are also far more differences between the living conditions in China and Japan and those in the West than just their intake of fats or their cholesterol levels.
This is an example of rubbish science! (was it funded by a statin manufacturing company?)
The advice to adopt a healthier diet is sound – until you read the actual recommended change. That isn't. If we are considering cancers, the works referenced below and those by Dr. Weston Price, Dr. Vilhjalmur Stefansson, Dr. Sir Robert McCarrison, and many more, show clearly that the change be made is away from Western-style processed foods, to a more natural diet.
Dr. Chris Hiley's suggestion that it is a 'Westernised high-fat diet that is to blame is almost certainly correct. But, then, a Westernised diet is high in polyunsaturated vegetable oils and processed margarines and cooking oils. These have been known to cause and promote cancers for well over 30 years.
We need to get the unnatural products out of our diet; cholesterol-lowering drugs are much more likely to exacerbate ill-health than to relieve it
References
1. Hutton, Dr. Samuel King. Health Conditions and Disease Incidence among the Eskimos of Labrador. Poole, England, 1925.
2. Amundsen, Roald. The Northwest Passage. London and New York, 1908.
3. Hoffman, Dr. Frederick L. The Mortality from Cancer Throughout the World. The Prudential Press, Newark, New Jersey, 1915.
4. Stefansson V. Cancer: Disease Of Civilization? Hill and Wang, New York, 1960
Last updated 29 August 2006
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