High cholesterol levels accelerate growth of prostate cancer

The findings, published in the April 1, 2005 issue of the Journal of Clinical Investigation, are in keeping with population studies that have linked prostate cancer with high cholesterol levels. The researchers also present evidence that cholesterol-lowering ‘statin’ drugs, now widely used in cardiovascular disease, may inhibit cancer growth.

A team led by Michael Freeman, Ph.D., program Director of the Urological Diseases Research Center at Children’s, injected human prostate cancer cells into mice and observed tumor growth. When the animals’ blood cholesterol was raised by diet, cholesterol accumulated in the outer membranes of the tumor cells. Cholesterol elevation in the membranes activated a chemical ‘cell-survival’ pathway known as Akt, thought to be a central pathway in prostate cancer. Activation of Akt enabled the tumor cells to resist chemical cues to commit suicide through the process known as apoptosis, thereby allowing the cancer to proliferate.

Increased cholesterol levels didn’t trigger new cancers in the mice, but they did result in a higher incidence of tumors and larger tumors.

In addition, test-tube studies showed that the use of the cholesterol-lowering drug simvastatin inhibited the Akt pathway, apoptosis increased, and tumors stopped proliferating. Replenishing cell membranes with cholesterol reversed this inhibitory effect.

‘Our study opens up a new paradigm in thinking about how cancer might be controlled pharmacologically by manipulating cholesterol,’ says Freeman. ‘Our data support the notion that cholesterol-lowering drugs might be effective in prevention of prostate cancer, or as an adjunctive therapy.’