Valproic acid targets IDH1 mutants through alteration of lipid metabolism.

ABSTRACT: Histone deacetylases (HDACs) have a wide range of targets and can rewire both the chromatin and lipidome of cancer cells. In this study, we show that valproic acid (VPA), a brain penetrant anti-seizure medication and histone deacetylase inhibitor, inhibits the growth of IDH1 mutant tumors in vivo and in vitro, with at least some selectivity over IDH1 wild-type tumors. Surprisingly, genes upregulated by VPA showed no enhanced chromatin accessibility at the promoter, but there was a correlation between VPA-downregulated genes and diminished promoter chromatin accessibility. VPA inhibited the transcription of lipogenic genes and these lipogenic genes showed significant decreases in promoter chromatin accessibility only in the IDH1 MT glioma cell lines tested. VPA inhibited the mTOR pathway an

SUBMITTER: Elahi LS 

PROVIDER: S-EPMC11321993 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature