The Effect of Dietary Molecule, Withaferin-A on Prostate Cancer

  • Chendil, Damodaran (PI)

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Prostate cancer is the most common malignancy in men and the third leading cause of cancer-related death in the US. The first line of treatment for metastatic prostate cancer is hormonal therapy using either androgen ablation therapy (MT) or bilateral orchidectomy. While most patients initially respond to M T. -30% have disease that is refractory to this treatment. Furthermore, a majority of the patients who initially respond to M T eventually relapse with androgen-independent prostate cancer (AIPC) within a 3-year period. The molecular mechanisms leading to AIPC are not clear and effective therapeutic agents for AIPC are not available. We have demonstrated that a dietary compound, Withaferin-A (WA), specifically targets AIPC cells by triggering (Par-4)-dependent apoptosis both in cell culture and animal models. A recent analysis of the critical molecular/genetic events in AIPC has revealed that over-expression of Akt, its downstream signaling mTOR leads to disease progression. A variety of transgenic mouse models have also demonstrated the cooperative roles of Akt and mTOR in AIPC progression. Although WA specifically targets AIPC, a detailed investigation of its mechanistic action on AIPC, particularly on Akt/mTOR-signaling pathway, is needed.
Effective start/end date7/1/105/31/11


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