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Cholesterol affects cancer survival


Lipid rafts are cholesterol- and sphingolipid-enriched microdomains in cell membranes that regulate phosphorylation cascades originating from membrane-bound proteins.
They are dynamic and continually aggregate and disaggregate.

Michael Freeman and colleagues from Children's Hospital Boston examined whether the cholesterol content of lipid rafts plays a role in prostate cancer.

The authors have showed that depletion of cholesterol by a cholesterol-lowering drug ( Simvastatin ) induces death of prostate cancer cells.
Elevating cholesterol content had the opposite effect, promoting tumor growth and decreasing death of the cancerous cells.
Thus, the cholesterol content of lipid rafts in cell membranes may mediate tumor survival and may be a potential target involved in tumor progression.

In this study, investigators 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 Akt/PKB pathway signaling, and induced apoptosis in LNCaP PCa cells.

Replenishing cell membranes with cholesterol reversed these inhibitory and apoptotic effects.

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.

Source: Journal of Clinical Investigation, 2005

XagenaMedicine_2005


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