Pharmacologic Ascorbate Primes Pancreatic Cancer Cells for Death by Rewiring Cellular Energetics and Inducing DNA Damage.

ABSTRACT: The clinical potential of pharmacologic ascorbate (P-AscH^-; intravenous delivery achieving mmol/L concentrations in blood) as an adjuvant in cancer therapy is being reevaluated. At mmol/L concentrations, P-AscH^- is thought to exhibit anticancer activity via generation of a flux of H₂O₂ in tumors, which leads to oxidative distress. Here, we use cell culture models of pancreatic cancer to examine the effects of P-AscH^- on DNA damage, and downstream consequences, including changes in bioenergetics. We have found that the high flux of H₂O₂ produced by P-AscH^- induces DNA damage. In response to this DNA damage, we observed that PARP1 is hyperactivated. Using our unique absolute quantitation, we found that P-

SUBMITTER: Buranasudja V 

PROVIDER: S-EPMC6774825 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature