title: Radioprotection of 4-hydroxy-3,5-dimethoxybenzaldehyde (VND3207) in culture cells is associated with minimizing DNA damage and activating Akt.
abstract: Vanillin is a naturally occurring compound and food-flavoring agent with antioxidant and antimutagenic activities. In present study, we explored the radioprotective effect of a novel vanillin derivative VND3207 (4-hydroxy-3,5-dimethoxybenzaldehyde). VND3207 has a much higher potential in scavenging hydroxyl radical and superoxide radical than vanillin as indicated in the ESR spin-trapping measurement, and it can effectively protect plasmid DNA against 10-50 Gy gamma-ray induced breaks in vitro at the concentrations as low as 10-20 microM. Using human lymphoblastoid AHH-1 cells and human fibroblastoid HFS cells, we demonstrated that VND3207 at 5-40 microM concentrations significantly attenuated the inhibition of proliferation and occurrence of apoptosis produced by 1-8 Gy gamma-irradiation. In the cultured cells, VND3207 significantly decreased the initial production and residual level of DNA double-strand breaks (DSBs) induced by 2 or 8 Gy irradiation. Treatment of VND3207 enhanced the level of DNA-PKcs protein, a critical component of DNA DSB repair pathway in the cells with or without gamma-irradiation. Consistently, the phosphorylation of Akt protein, a mediator of survival signal, as well as its substrate GSK3beta was concurrently increased by VND3207. Our results suggest that VND3207 has radioprotection effect through its capabilities as a powerful antioxidant, in minimizing DNA damage, and activating survival signal Akt pathway, and it may be of value in the development of radioprotective compounds.
authors.affiliation: Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.forename: Zhi-Wu
authors.initials: ZW
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Si-Ying
authors.initials: SY
authors.lastname: Wang
authors.forename: Yu-Qian
authors.initials: YQ
authors.lastname: Yan
authors.forename: Ke
authors.initials: K
authors.lastname: Wu
authors.forename: Qin-Zhi
authors.initials: QZ
authors.lastname: Xu
authors.forename: Shi-Meng
authors.initials: SM
authors.lastname: Zhang
authors.forename: Ping-Kun
authors.initials: PK
authors.lastname: Zhou
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001547:Benzaldehydes / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D002478:Cells, Cultured; D020552:Comet Assay / Q000379:methods; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects / Q000528:radiation effects; D053904:DNA Breaks, Single-Stranded / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D008297:Male; D015394:Molecular Structure; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011837:Radiation-Protective Agents / Q000737:chemistry / Q000494:pharmacology*; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects
chemical_list: C506569:4-hydroxy-3,5-dimethoxybenzaldehyde; D000975:Antioxidants; D001547:Benzaldehydes; C514503:GSKIP protein, human; D011837:Radiation-Protective Agents; D012097:Repressor Proteins; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases