Novel dual-action prodrug triggers apoptosis in glioblastoma cells by releasing a glutathione quencher and lysine-specific histone demethylase 1A inhibitor.

ABSTRACT: Targeting epigenetic mechanisms has shown promise against several cancers but has so far been unsuccessful against glioblastoma (GBM). Altered histone 3 lysine 4 methylation and increased lysine-specific histone demethylase 1A (LSD1) expression in GBM tumours nonetheless suggest that epigenetic mechanisms are involved in GBM. We engineered a dual-action prodrug, which is activated by the high hydrogen peroxide levels associated with GBM cells. This quinone methide phenylaminecyclopropane prodrug releases the LSD1 inhibitor 2-phenylcyclopropylamine with the glutathione scavenger para-quinone methide to trigger apoptosis in GBM cells. Quinone methide phenylaminocyclopropane impaired GBM cell behaviours in two-dimensional and three-dimensional assays, and triggered cell apoptosis in several p

SUBMITTER: Engel M 

PROVIDER: S-EPMC6590141 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature