Curcumin confers radiosensitizing effect in prostate cancer cell line PC-3

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Abstract
Curcumin (Diferuloylmethane) is a major chemical component of turmeric (curcuma longa) and is used as a spice to give a specific flavor and yellow color in Asian food. Curcumin exhibits growth inhibitory effects in a broad range of tumors as well as in TPA-induced skin tumors in mice. This study was undertaken to investigate the radiosensitizing effects of curcumin in p53 mutant prostate cancer cell line PC-3. Compared to cells that were irradiated alone (SF2=0.635; D0=231 cGy), curcumin at 2 and 4 M concentrations in combination with radiation showed significant enhancement to radiation-induced clonogenic inhibition (SF2=0.224: D0=97 cGy and SF2=0.080: D0=38 cGy) and apoptosis. It has been reported that curcumin inhibits TNF--induced NFB activity that is essential for Bcl-2 protein induction. In PC-3 cells, radiation upregulated TNF- protein leading to an increase in NFB activity resulting in the induction of Bcl-2 protein. However, curcumin in combination with radiation treated showed inhibition of TNF--mediated NFB activity resulting in bcl-2 protein downregulation. Bax protein levels remained constant in these cells after radiation or curcumin plus radiation treatments. However, the downregulation of Bcl-2 and no changes in Bax protein levels in curcumin plus radiation-treated PC-3 cells, together, altered the Bcl2 : Bax ratio and this caused the enhanced radiosensitization effect. In addition, significant activation of cytochrome c and caspase-9 and -3 were observed in curcumin plus radiation treatments. Together, these mechanisms strongly suggest that the natural compound curcumin is a potent radiosesitizer, and it acts by overcoming the effects of radiation-induced prosurvival gene expression in prostate cancer.