Curcumin inhibits NFkappaB mediated radioprotection and modulate apoptosis related genes in human neuroblastoma cells.
Curcumin has been shown to exhibit growth inhibitory effects and induce apoptosis in a broad range of tumors. Accordingly, we investigated the radiosensitizing effects of curcumin in human neuroblastoma cells. SK-N-MC cells exposed to either 2 Gy alone, or pretreated with curcumin (100 nM) or NFkappaB inhibitor peptide SN50 (50 nM) and exposed to 2 Gy were harvested after 48 h. Radioresistance was measured using clonogenic and MTT assay, NFkappaB DNA-binding activity using electrophoretic mobility shift assay, and apoptosis using Annexin V-FITC staining. Pathway (apoptosis) specific microarrays were used to measure gene expression and validated using QPCR. Radiation markedly enhanced the NFkappaB DNA-binding activity. Pre-treating the cells either with curcumin or SN50 significantly suppressed the radiation induced NFkappaB. Also, curcumin or SN50 pretreatment enhanced the radiation induced inhibition of cell survival. Microarray analysis revealed that curcumin enhanced the radiation induced activation of caspases, other pro-apoptotic and death effector molecules and, inhibit anti-apoptotic/survival molecules. In addition, curcumin markedly suppressed the radiation induced TNF super family genes. These results suggest that curcumin is a potent radiosensitizer and may act by overcoming the effects of radiation-induced NFkappaB mediated pro-survival gene expression in neuroblastoma.
Aravindan
Natarajan
N
Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA. naravind@ouhsc.edu
Madhusoodhanan
Rakhesh
R
Ahmad
Salahuddin
S
Johnson
Daniel
D
Herman
Terence S
TS
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004789:Enzyme Activation; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000528:radiation effects; D009447:Neuroblastoma / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000494:pharmacology; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D016328:NF-kappa B; D010455:Peptides; D011838:Radiation-Sensitizing Agents; C118258:SN50 peptide; D004247:DNA; D020169:Caspases; D003474:Curcumin