Targeting prostate cancer by inhibition of mTOR with ezhu oil

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DESCRIPTION (provided by applicant): Prostate cancer is the third leading cause of cancer death of males in the United States. The common treatments for prostate cancer, hormone ablation and endocrine therapy, lead to temporary palliation. Identification of other novel molecular targets independent of androgen receptor would lead to the development of new effective therapeutic agents. Advances in molecular genetics have identified that PI3K/Akt/mTOR signaling pathway mediates cellular proliferation and survival and that is activated in prostate cancer. The mTOR signaling is a prime target for development of therapeutic agents for treating prostate cancer. Ezhu oil, the essential oil isolated from Curcuma, has been used as a traditional Chinese medicine to treat virus infections and cancers. Ezhu oil and one of its components, curcumol, inhibit prostate cancer cell growth and the mTOR-signaling pathway. We hypothesize that ezhu oil which might contain novel mTOR signaling inhibitors could be used as a therapeutic agent or in combination with known mTOR inhibitor rapamycin analogue CCI-779 as a complementary therapeutic medicine for prostate cancer treatment. We propose 1): to identify the active components of ezhu oil which inhibit mTOR signaling and to standardize ezhu oil based on the active component(s); 2): to investigate the roles of the mTOR signaling pathway in ezhu oil- and curcumol-inhibited prostate cancer cell growth and to determine the combined effects of ezhu oil or curcumol with CCI-779 in prostate cancer cells; 3) to determine the efficacies of ezhu oil and curcumol alone or in combination with CCI-779 in vivo in xenografts. We hope our application will lead to the discovery of a novel complementary agent for prostate cancer treatment based on the specific molecular targets. PUBLIC HEALTH RELEVANCE: This application will investigate the growth inhibitory effect of ezhu oil, a traditional Chinese medicine, and to identify the mechanism of action and the active components. The purpose of this application hopes to establish a rational for improving the therapeutic outcome of complementary and alternative medicines based on specific molecular targets in prostate cancer.