title: Vanillin derivative 6-bromine-5-hydroxy-4-methoxybenzaldehyde-elicited apoptosis and G2/M arrest of Jurkat cells proceeds concurrently with DNA-PKcs cleavage and Akt inactivation.
abstract: Vanillin, a naturally occurring food component, has been reported to have anti-mutagenic and anti-metastatic potentials, and to inhibit DNA-PKcs activity. However, vanillin itself exhibits very weak antiproliferative activity. We explored the effects of bromovanin (6-bromine-5-hydroxy-4-methoxybenzaldehyde), a novel vanillin derivative, on survival and cell-cycle progression of human Jurkat leukemia cells. Treatment with >10 microM bromovanin significantly elicited apoptosis and G2/M arrest in Jurkat cells in a dose- and time-dependent manner. Bromovanin-induced DNA double-strand breaks (DSB) were demonstrated by means of comet assay as well as detection of phosphorylated H2AX, a sensitive indicator of DNA DSBs. Immuno-hybridization analysis revealed that the cleavage of procaspase-3 and DNA-PKcs occurred concurrently with bromovanin-induced apoptosis. Furthermore, phosphorylated Akt protein (Ser473), which is catalyzed by DNA-PKcs, as well as phosphorylated GSK3beta (a substrate of activated Akt), markedly decreased in bromovanin-treated Jurkat cells, suggesting that bromovanin leads to inactivation of Akt pathway via cleaving DNA-PKcs. These multiple effects, associated with the regimen of cancer therapeutic strategies, make bromovanin very appealing for future development as a novel anticancer drug.
authors.affiliation: Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China.
authors.forename: Yu-Qian
authors.initials: YQ
authors.lastname: Yan
authors.forename: Qin-Zhi
authors.initials: QZ
authors.lastname: Xu
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Jian-Li
authors.initials: JL
authors.lastname: Sui
authors.forename: Bei
authors.initials: B
authors.lastname: Bai
authors.forename: Ping-Kun
authors.initials: PK
authors.lastname: Zhou
mesh_terms: D017209:Apoptosis; D001547:Benzaldehydes / Q000737:chemistry* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D051747:DNA-Activated Protein Kinase / Q000187:drug effects*; D006801:Humans; D019169:Jurkat Cells; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*
chemical_list: D001547:Benzaldehydes; C515564:bromovanin; D004247:DNA; C100058:vanillin; D051747:DNA-Activated Protein Kinase; D051057:Proto-Oncogene Proteins c-akt