title: Curcumin confers protection to irradiated THP-1 cells while its nanoformulation sensitizes these cells via apoptosis induction.
abstract: Protection against ionizing radiation (IR) and sensitization of cancer cells to IR are apparently contrasting phenomena. However, curcumin takes on these contrasting roles leading to either protection or enhanced apoptosis in different irradiated cells. Here we studied whether pretreatment with free curcumin or a novel dendrosomal nanoformulation of curcumin (DNC) could exert protective/sensitizing effects on irradiated THP-1 leukemia cells. We employed assays including MTT viability, clonogenic survival, DNA fragmentation, PI/Annexin V flow cytometry, antioxidant system (ROS, TBARS for lipid peroxidation, 8-OHdG and γH2AX for DNA damage, glutathione, CAT and GPx activity, enzymes gene expression), ELISA (NF-κB and Nrf2 binding, TNF-α release), caspase assay, siRNA silencing of caspase-3, and western blotting to illustrate the observed protective role of curcumin in comparison with the opposite sensitizing role of its nanoformulation at a similar 10 μM concentration. The in vivo relevance of this concentration was determined via intraperitoneal administration in mice. Curcumin significantly enhanced the antioxidant defense, while DNC induced apoptosis and reduced viability as well as survival of irradiated THP-1 cells. Nrf2 binding showed an early rise and fall in DNC-treated cells, despite a gradual increase in curcumin-treated cells. We also demonstrated that DNC induced apoptosis in THP-1 cells via caspase-3 activation; whereas in combination with radiation, DNC alternatively employed a caspase-independent apoptosis pathway involving cytochrome c release from mitochondria.
authors.affiliation: Department of Biotechnology, College of Science, University of Tehran, Enghelab St., Tehran, 14155-6455, Iran.
authors.forename: Behrooz
authors.initials: B
authors.lastname: Soltani
authors.affiliation: Department of Biotechnology, College of Science, University of Tehran, Enghelab St., Tehran, 14155-6455, Iran. nasser.ghaemi@khayam.ut.ac.ir.|School of Chemistry, College of Science, University of Tehran, Tehran, Iran. nasser.ghaemi@khayam.ut.ac.ir.
authors.forename: Nasser
authors.initials: N
authors.lastname: Ghaemi
authors.affiliation: Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Sadeghizadeh
authors.affiliation: Department of Resin and Additives, Institute for Color Science and Technology, Tehran, Iran.
authors.forename: Farhood
authors.initials: F
authors.lastname: Najafi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D019610:Cytoprotection / Q000187:drug effects* / Q000528:radiation effects; D053938:DNA Fragmentation / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008055:Lipids / Q000737:chemistry; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D053758:Nanoparticles / Q000737:chemistry*; D009336:Necrosis; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D008055:Lipids; D003474:Curcumin
keywords: Apoptosis; Cytochrome c; GSH; Nrf2; Radiation; TNF-α