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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.

international journal of oncology

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