title: Curcumin and trans-resveratrol exert cell cycle-dependent radioprotective or radiosensitizing effects as elucidated by the PCC and G2-assay.
abstract: Curcumin and trans-resveratrol are well-known antioxidant polyphenols with radiomodulatory properties, radioprotecting non-cancerous cells while radiosensitizing tumor cells. This dual action may be the result of their radical scavenging properties and their effects on cell-cycle checkpoints that are activated in response to radiation-induced chromosomal damage. It could be also caused by their effect on regulatory pathways with impact on detoxification enzymes, the up-regulation of endogenous protective systems, and cell-cycle-dependent processes of DNA damage. This work aims to elucidate the mechanisms underlying the dual action of these polyphenols and investigates under which conditions they exhibit radioprotecting or radiosensitizing properties. The peripheral blood lymphocyte test system was used, applying concentrations ranging from 1.4 to 140μM curcumin and 2.2 to 220μM trans-resveratrol. The experimental design focuses first on their radioprotective effects in non-cycling lymphocytes, as uniquely visualized using cell fusion-mediated premature chromosome condensation, excluding, thus, cell-cycle interference to repair processes and activation of checkpoints. Second, the radiosensitizing potential of these chemicals on the induction of chromatid breaks in cultured lymphocytes following G2-phase irradiation was evaluated by a standardized G2-chromosomal radiosensitivity predictive assay. This assay uses caffeine for G2-checkpoint abrogation and it was applied to obtain an internal control for radiosensitivity testing, which simulates conditions similar to those of the highly radiosensitive lymphocytes of AT patients. The results demonstrate for the first time the cell-cycle-dependent action of these polyphenols. When non-cycling cells are irradiated, the radioprotective properties of curcumin and trans-resveratrol are more prominent. However, when cycling cells are irradiated during G2-phase, the radiosensitizing features of these compounds are more pronounced. This observation offers a new biological basis for the mechanisms underlying the action of these polyphenols in cancer radiotherapy.
authors.affiliation: Radiation Protection Service, IIS La Fe, Health Research Institute La Fe, Valencia, Spain. Electronic address: natividad.sebastia@uv.es.
authors.forename: N
authors.initials: N
authors.lastname: Sebastià
authors.affiliation: Radiation Protection Service, Universitary and Politechnic Hospital La Fe, Valencia, Spain; Grupo de Investigación Biomédica en Imagen GIBI230, IIS La Fe, Health Research Institute La Fe, Valencia, Spain; Unidad Mixta de Investigación en Endocrinología, Nutrición y Dietética Clínica, IIS La Fe, Health Research Institute La Fe, Valencia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Montoro
authors.affiliation: Biostatistics Unit, IIS La Fe, Health Research Institute La Fe, Valencia, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Hervás
authors.affiliation: Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Centre for Scientific Research "Demokritos", Aghia Paraskevi, Athens, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Pantelias
authors.affiliation: Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Centre for Scientific Research "Demokritos", Aghia Paraskevi, Athens, Greece.
authors.forename: V I
authors.initials: VI
authors.lastname: Hatzi
authors.affiliation: Grupo de Investigación Biomédica en Imagen GIBI230, IIS La Fe, Health Research Institute La Fe, Valencia, Spain; Unidad Mixta de Investigación en Endocrinología, Nutrición y Dietética Clínica, IIS La Fe, Health Research Institute La Fe, Valencia, Spain; Department of Preventive Medicine and Public Health, Faculty of Pharmacy, University of Valencia, Burjassot, Valencia, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Soriano
authors.affiliation: Radiation Protection Service, Universitary and Politechnic Hospital La Fe, Valencia, Spain.
authors.forename: J I
authors.initials: JI
authors.lastname: Villaescusa
authors.affiliation: Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Centre for Scientific Research "Demokritos", Aghia Paraskevi, Athens, Greece.
authors.forename: G I
authors.initials: GI
authors.lastname: Terzoudi
mesh_terms: D000818:Animals; D016466:CHO Cells; D002453:Cell Cycle / Q000187:drug effects; D002459:Cell Fusion; D002478:Cells, Cultured; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D003474:Curcumin / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D009152:Mutagenicity Tests; D011836:Radiation Tolerance / Q000187:drug effects; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D011837:Radiation-Protective Agents; D011838:Radiation-Sensitizing Agents; D013267:Stilbenes; D003474:Curcumin; D000077185:Resveratrol
keywords: Curcumin; G2-assay; Premature chromosome condensation; Radioprotector; Radiosensitizer; trans-Resveratrol