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

• Published in: Oncogene Vol. 23; no. 8; pp. 1599 - 1607
• Main Authors: CHENDIL, Damodaran, RANGA, Rama S, MEIGOONI, David, SATHISHKUMAR, Sabapathi, AHMED, Mansoor M
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 26.02.2004; Nature Publishing Group
• Subjects: Apoptosis; Apoptosis - radiation effects; Bax protein; Bcl-2 protein; Biological and medical sciences; Caspase-9; Caspases - genetics; Caspases - metabolism; Cell Line, Tumor; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Combined Modality Therapy; Curcuma longa; Curcumin; Curcumin - pharmacology; Cyclin D1 - antagonists & inhibitors; Cyclin D1 - radiation effects; Cytochrome c; Cytochromes c - metabolism; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation, Neoplastic - radiation effects; Gynecology. Andrology. Obstetrics; Humans; Male; Male genital diseases; Medical sciences; Molecular and cellular biology; Nephrology. Urinary tract diseases; NF-kappa B - drug effects; NF-kappa B - radiation effects; NF-κB protein; p53 Protein; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - radiotherapy; Proteins; Radiation; Radiation therapy; Radiation Tolerance; Radiation, Ionizing; Radiation-Sensitizing Agents - pharmacology; Radiosensitization; Tumor Necrosis Factor-alpha - pharmacology; Tumor necrosis factor-α; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Bcl-2; Urinary system disease; Prostate disease; NFκB; Cytokine; Malignant tumor; Carcinogenesis; Cell line; TNF-α; Tumor necrosis factor; radiation; C-Onc gene; Irradiation; prostate; Male genital diseases; Prostate cancer; Protooncogene; Apoptosis; curcumin
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1207284

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 (SF(2)=0.635; D(0)=231 cGy), curcumin at 2 and 4 microM concentrations in combination with radiation showed significant enhancement to radiation-induced clonogenic inhibition (SF(2)=0.224: D(0)=97 cGy and SF(2)=0.080: D(0)=38 cGy) and apoptosis. It has been reported that curcumin inhibits TNF-alpha-induced NFkappaB activity that is essential for Bcl-2 protein induction. In PC-3 cells, radiation upregulated TNF-alpha protein leading to an increase in NFkappaB activity resulting in the induction of Bcl-2 protein. However, curcumin in combination with radiation treated showed inhibition of TNF-alpha-mediated NFkappaB 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.