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S1P as a target for chemoprevention ?

Chemoprevention involving the use of natural agents to suppress, block or reverse the process of carcinogenesis could be an effective approach to reduce the incidence of prostate cancer. This cancer represents an excellent candidate disease for chemoprevention, as it is typically diagnosed in elderly men. Even a modest delay in the neoplastic development achieved through pharmacological or therapeutic intervention could result in substantial reduction in the incidence of the clinically detectable disease.

There is intense activity in defining chemopreventive agents and molecular targets for prostate cancer chemoprevention. Studies conducted on cell-culture systems and animal models as well as human epidemiological studies show that the polyphenols (notably EGCg) that are present in green tea could afford protection against a variety of cancer types including prostate cancer. Based on the observation that SphK1 is overexpressed in prostate cancer patients, it was of interest to study the effects on SphK1 of « nutraceuticals » like green tea. Pure EGCg or a mixture of polyphenols from green tea trigger a strong down-regulation of SphK1 activity and apoptosis in multiple prostate cancer cell lineages, an effect blocked by SphK1 overexpression.

Pre-clinical studies in nude mice fed with drinking water containing pure EGCg or mixture of polyphenols then xenotransplanted (ortho- or heterotopically) with fluorescent prostate cancer cells confirmed these in vitro observations. The down-regulation of SphK1 in vivo was associated with a marked decrease in primary tumor size as well as a strong diminution of metastasis spreading. Similar studies have been carried out with similar results with other polyphenols : resveratrol and derivatives (Brizuela-Madrid et al., Faseb J, 2010).

 

Public release from the Federation of American Societies for Experimental Biology (FASEB) : June 9, 2010