Pharmacometabolomics Reveals Irinotecan Mechanism of Action in Cancer Patients.

ABSTRACT: The purpose of this study was to identify early circulating metabolite changes implicated in the mechanism of action of irinotecan, a DNA topoisomerase I inhibitor, in cancer patients. A liquid chromatography-tandem mass spectrometry-based targeted metabolomic platform capable of measuring 254 endogenous metabolites was applied to profile circulating metabolites in plasma samples collected pre- and post-irinotecan treatment from 13 cancer patients. To gain further mechanistic insights, metabolic profiling was also performed for the culture medium of human primary hepatocytes (HepatoCells) and 2 cancer cell lines on exposure to SN-38 (an active metabolite of irinotecan). Intracellular reactive oxygen species (ROS) was detected by dihydroethidium assay. Irinotecan induced a global metabolic

SUBMITTER: Bao X 

PROVIDER: S-EPMC6857457 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature