A framework for large-scale dynamic metabolome drug profiling in mammalian cells: a case study analysis of the anti-cancer drug dichloroacetate

摘要: Metabolic profiling of cell line collections have become an invaluable tool to study disease etiology, drug modes action and personalized medicine. However, large-scale in vitro dynamic metabolic is limited by time-consuming sampling complex measurement procedures. By adapting MS-based metabolomics workflow for high-throughput diverse adherent mammalian cells, we establish a technique the rapid analysis drug-induced changes intracellular metabolites. This methodology scalable large compound libraries here applied mechanism underlying toxic effect dichloroacetate ovarian cancer lines. System-level responses revealed key unexpected role CoA imbalance toxicity. The herein proposed strategy complementary other molecular techniques, opening new scientific drug-discovery opportunities.