Radiosensitizing Potential of Curcumin in Different Cancer Models

Over the past decades, studies of phytochemicals as modifiers of radiotherapeutic efficacy have become increasingly popular to improve the treatment outcome of human malignancies. In the current comprehensive review article, radiosensitizing effects of curcumin, a yellow-colored polyphenolic constituent of turmeric, in various preclinical cancer models, both In Vitro and In Vivo, are presented. Attenuation of radioadaptation and augmentation of irradiation-induced cancer cell killing are achieved through multifaceted action of curcumin on suppression of prosurvival and antiapoptotic factors. Most importantly, curcumin can block radiation-triggered NF-κB signaling pathway and downregulate downstream effector proteins, thereby conferring potentiation of radioresponses. Based on the elucidated molecular mechanisms but also due to its safety profile and low cost, curcumin might be considered a promising adjuvant agent to enhance radiotherapeutic efficacy in the treatment of various cancer types formed in different human organ systems. Further efforts to translate the current preclinical knowledge to the real application of curcumin in combinatorial radiotherapeutic strategies in clinical settings are necessary.AbbreviationsAKTprotein kinase BARMSalveolar rhabdomyosarcomaATMataxia telangiectasia mutatedBaxBcl-2-associated X proteinBcl-2B-cell lymphoma 2CDC2cyclin-dependent kinase 2Bcl-xLB-cell lymphoma-extra largec-FLIPcellular FLICE-like inhibitory proteinCDDPcisplatinCOX-2cyclooxygenase-2cyt ccytochrome cDNA-PKcsDNA-dependent protein kinaseEGFRepidermal growth factor receptorEMTepithelial-mesenchymal transitionERKextracellular signal-regulated kinaseESEwing`s sarcomaETS2erythroblastosis virus transcription factor 2GBMglioblastoma multiformeHCChepatocellular carcinomaHNSCChead and neck squamous cell carcinomaIAPinhibitor of apoptosis proteinIκBαinhibitor of κB alphaIKKinhibitor of κB kinaseIRionizing radiationlncRNAlong non-coding RNAlucluciferaseMcl-1myeloid cell leukemia-1MDR1multidrug resistance protein 1miRmicroRNAMMP-9matrix metalloproteinase-9mTORmammalian target of rapamycinNBneuroblastomaNF-κBnuclear factor-κBNPCnasopharyngeal carcinomaNSCLCnon-small cell lung cancerOSCCoral squamous cell carcinomaPARPpoly-(ADP-ribose)-polymerasepH2AXphosphorylated histone 2AX-immunoreactivePI3Kphosphatidylinositol 3-kinasePrp4KPre-mRNA processing factor 4 kinaseRCCrenal cell carcinomaROSreactive oxygen speciesSCCsquamous cell carcinomaSLNsolid lipid nanoparticleSOD2superoxide dismutase 2TERTtelomerase reverse transcriptaseTNF-αtumor necrosis factor-αTxnRd1thioredoxin reductase-1VEGFvascular endothelial growth factorXIAPX-linked inhibitor of apoptosis proteinΔΨmmitochondrial membrane potential.