Inhibition of Radiation Induced Prosurvival Proteins by Curcumin in Prostate Cancer

Prostate cancer is one of the major life-threatening diseases among male population in the Western WorId. One of the important aspects in the treatment of cancer is to kill the cancer cells by chemotherapeutic agents or radiation. Most of the tumors are resistant to many therapeutic agents due to their complicated genetic make-up that cause resistance to treatment. So, till to date, there is no effective treatment modality once the prostate cancer is not response to hormones. The prospect of current conventional cancer therapies are painful, devastating and it mayor may not prolong survival. So it is very important to identify anti cancer agents that are non-toxic but highly effective to induce cell death preferentially in tumor cells. This can potentially lead to novel alternative therapies in the management of prostate cancer. Prostate tumors are radiation resistant because of two reasons. (1) Most of tumor suppressing genes lose their function and genes involved in cell death function are not active. (2) Due to lack of these functions in these key genes, the prostate tumor cells produce certain factors (called proteins) when exposed to radiation that keep them alive and protect them from the radiation-killing effects. Our preliminary experiments showed that radiation induces two obvious factors in prostate cancer cells, that is the anti-cell death protein Bcl-2 and NFKB activity (an inducer ofBcl-2 gene) that cause tumor cells resistant to radiation as well as chemotherapy. Curcumin is a major chemical component of turmeric and used as a spice to give a specific flavor and yellow color in Asian food. Curcumin has been reported to have several effects including anti-tumor properties and inhibit broad range of tumors in human. Our preliminary results showed that Curcumin was found to inhibit these radiation induce pro-survival proteins such as NFKB and Bcl-2 in human prostate tumor cells and thus enhance the cell killing effect of radiation. Hence, in this study, we wanted to put Curcumin in prostate tumor cells grown in laboratory and expose it to radiation and evaluate the killing response. Interestingly, we also found that when we put Curcumin in prostate cancer cells, cell-killing proteins do not go up and further enhances the killing effect of radiation. This made us to believe that Curcumin mediates its' cell killing effect on prostate cancer cells through inhibition of pro survival genes. In this project, we would like to understand the effect of Curcumin on prostate cancer as a sensitizer of radiation, since it has the advantage of being a nontoxic natural product. Overall, in this proposal we are showing sufficient evidence that the naturally occurring compound Curcumin could be potentially used for the treatment of prostate cancer.