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

Oncogene volume 23, pages 1599–1607 (2004)Cite this article

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 μ 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-α-induced NFκB activity that is essential for Bcl-2 protein induction. In PC-3 cells, radiation upregulated TNF-α protein leading to an increase in NFκB activity resulting in the induction of Bcl-2 protein. However, curcumin in combination with radiation treated showed inhibition of TNF-α-mediated NFκB 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.

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Acknowledgements

This work is supported by DOD PC020620 to DC.

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Authors and Affiliations

  1. Department of Clinical Science, University of Kentucky, Lexington, 40536, KY, USA

    Damodaran Chendil, Rama S Ranga & David Meigooni

  2. Department of Radiation Medicine, University of Kentucky, Lexington, 40536, KY, USA

    Sabapathi Sathishkumar & Mansoor M Ahmed

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  1. Damodaran Chendil
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  2. Rama S Ranga
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Correspondence to Damodaran Chendil.

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Chendil, D., Ranga, R., Meigooni, D. et al. Curcumin confers radiosensitizing effect in prostate cancer cell line PC-3. Oncogene 23, 1599–1607 (2004). https://doi.org/10.1038/sj.onc.1207284

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