Curcumin confers radiosensitizing effect in prostate cancer cell line PC-3.
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.
Chendil
Damodaran
D
Department of Clinical Science, University of Kentucky, Lexington, KY 40536, USA. dchen2@uky.edu
Ranga
Rama S
RS
Meigooni
David
D
Sathishkumar
Sabapathi
S
Ahmed
Mansoor M
MM
D017209:Apoptosis / Q000528:radiation effects; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D003474:Curcumin / Q000494:pharmacology*; D019938:Cyclin D1 / Q000037:antagonists & inhibitors / Q000528:radiation effects; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000187:drug effects / Q000528:radiation effects; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy*; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016328:NF-kappa B; D011838:Radiation-Sensitizing Agents; D014409:Tumor Necrosis Factor-alpha; D019938:Cyclin D1; D045304:Cytochromes c; D020169:Caspases; D003474:Curcumin