Inhibition of Radiation Induced Pro-Survival Genes by Curcumin in Prostate Cancer

摘要

In prostate cancer, constitutive activation of NFkB and Apt, non- functional p53 and defective androgen receptor signaling together may play a role in rendering intrinsic resistance to radiation in prostate cancer. Many reports in literature have showed that Curcumin (diferulylmethane is a major chemical component of a curry spice, turmeric) is a potent inhibitor of prostate cancer cell growth. It was found that Curcumin inhibits TNF-alpha mediated activation of NFKB and down-regulates Bcl-2 expression. From this reported observation, we hypothesized that Curcumin will abrogated the upregulation of pro-survival genes by radiation. Our preliminary data demonstrated that Curcumin significantly inhibited the growth of androgen- independent prostate cancer cell line PC-3. In addition, Curcumin conferred significant enhancement of radiation-induced clonogenic inhibition and apoptosis in prostate cancer cell line PC-3. Interestingly, Curcumin also inhibited the radiation induced prosurvival factors such as NFKB activity and Bcl-2 expression. These results underscore the need to formally study the functional relevance of Curcumin in synergizing the effects of radiation in prostate cancer. Since the proposal was funded for two years and the Pt was asked to drop aim 3 and request to resubmit the aims. Hence, the first aim is completed in the proposed time.