Inhibition of Prostate Carcinogenesis by Apigenin

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DESCRIPTION (provided by applicant): Prostate cancer is the most common and one of the leading causes of cancer-related deaths in American males. To reduce the incidence of this disease, chemoprevention through dietary intervention appears to be an encouraging approach. Epidemiological studies suggest that high consumption of fruits and vegetables may be associated with a reduced risk of prostate cancer. These studies are consistent with the observations that Asian men who consume low fat, high-fiber diet rich in flavonoids have lowest prostate cancer incidence in the world. Laboratory studies in cell culture systems have demonstrated that apigenin, a common flavonoid present in fruits and vegetables afford protection against many types of epithelial cancers including skin, colon, and breast. Consistent with this notion, our recent studies (BBRC 287:914-20, 2001 & Oncogene, In Press) are noteworthy where we have shown i) selective response of apigenin against normal versus prostate carcinoma cells, ii) inhibition of cell growth, iii) induction of apoptosis in a wide range of human prostate carcinoma cells. An important implication of these findings could be that apigenin may have preventive effects against the development of prostate cancer in humans. This could be an effective prevention by delay. If this occurs then apigenin can slow the process of cancer cell growth in humans, it will be important for the survival and quality of life of patients diagnosed with prostate cancer at an early stage. However, these associations remain inconclusive because there is no such study conducted so far which could provide evidence-based prevention and intervention of apigenin on prostate carcinogenesis. In the present application, we will test this hypothesis in a recently developed transgenic animal model TRAMP (transgenic adenocarcinoma mouse prostate) that mimics progressive forms of human prostatic disease. The central hypothesis to be tested in this application is that apigenin will impart cancer-preventive and possibly cancer-therapeutic effect by modulating the apoptotic machinery of prostate cancer cells in TRAMP model of prostate carcinogenesis. Both in vivo tumor growth and apoptosis will be monitored serially during the experimental protocol by our recently perfected technique of MRI and 99M-Tc-labeled annexin V. A successful completion of this application will set a platform to define the role of apigenin as a promising agent against prevention and possibly therapy of prostate cancer in humans.