Pharmacologic Ascorbate and DNMT Inhibitors Increase DUOX Expression and Peroxide-Mediated Toxicity in Pancreatic Cancer.

ABSTRACT: Recent studies have demonstrated an important role for vitamin C in the epigenetic regulation of cancer-related genes via DNA demethylation by the ten-eleven translocation (TET) methylcytosine dioxygenase enzymes. DNA methyltransferase (DNMT) reverses this, increasing DNA methylation and decreasing gene expression. Dual oxidase (DUOX) enzymes produce hydrogen peroxide (H₂O₂) in normal pancreatic tissue but are silenced in pancreatic cancer (PDAC). Treatment of PDAC with pharmacologic ascorbate (P-AscH^-, intravenous, high dose vitamin C) increases DUOX expression. We hypothesized that inhibiting DNMT may act synergistically with P-AscH^- to further increase DUOX expression and cytotoxicity of PDAC. PDAC cells demonstrated dose-dependent increases i

SUBMITTER: Steers GJ 

PROVIDER: S-EPMC10525653 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature