Evaluation of the cytotoxic and growth inhibitory effects and synergism of natural plant-derived mixtures in prostate cancer cells.

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The objective of this proposal is to determine the potential anticancer actions of six natural plant-derived extracts by determining their ability to kill prostate cancer cells or inhibit their growth. Prostate cancer is an important burden on society as it is the most frequent cancer diagnosed in men and the second leading cause of cancer-related death of the aging male. Prostate cancer is usually initially androgen-dependent and treatable with antiandrogen therapy. However, often prostate cancer progresses to an androgen-independent state that is drug-resistant and poorly treatable, resulting in metastases and death of the patient. The frequency of prostate cancer is strongly influenced by nutrition, with a diet high in plant-derived foods acting protectively. The long latency period in the development of prostate tumors makes this disease particularly suitable for targeting by nutritional supplements, such as natural plant extracts. We propose to determine the ability of six plant extracts to kill prostate cancer cells with properties reflecting various stages of the disease, including early-stage androgen-dependent and late-stage androgen-independent tumor cells. The plant extracts will be supplied by our collaborating company Idunn Technologies. The cellular mechanisms of cell death will be investigated to determine exactly how the plant extracts kill the cells. In addition, various mixtures of natural plant-derived extracts will be tested to determine potential synergistic effects on prostate cancer cell death. If it is found that different plant extracts kill prostate cancer cells via different cell death pathways, it is possible that a combined exposure to two or more extracts may result in greater than additive effects; this approach may also prevent tumor cells from gaining resistance against on single treatment. The findings of this proposal will provide essential information on the potential for certain plant extracts or mixtures of these extracts to act as effective chemopreventive or chemotherapeutic agents, particularly in the fight against drug-resistant prostate cancer.