Decreased Levels of GSH Are Associated with Platinum Resistance in High-Grade Serous Ovarian Cancer.

ABSTRACT: High-grade serous ovarian cancer (HGSOC) is the most common and aggressive OC histotype. Although initially sensitive to standard platinum-based chemotherapy, most HGSOC patients relapse and become chemoresistant. We have previously demonstrated that platinum resistance is driven by a metabolic shift toward oxidative phosphorylation via activation of an inflammatory response, accompanied by reduced cholesterol biosynthesis and increased uptake of exogenous cholesterol. To better understand metabolic remodeling in OC, herein we performed an untargeted metabolomic analysis, which surprisingly showed decreased reduced glutathione (GSH) levels in resistant cells. Accordingly, we found reduced levels of enzymes involved in GSH synthesis and recycling, and compensatory increased expression of th

SUBMITTER: Criscuolo D 

PROVIDER: S-EPMC9404763 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature