Downregulation of neutral ceramidase by gemcitabine: Implications for cell cycle regulation.

ABSTRACT: Gemcitabine (GMZ) is a chemotherapeutic agent with well established effects on cell growth arrest and apoptosis. In this study, we investigated the potential roles of bioactive sphingolipids in mediating the growth suppressing effects of GMZ on a polyoma middle T transformed murine endothelial cell line. After 12-hour GMZ (0.6 microM) treatment, cell growth was arrested at the G(0)/G(1) phase as detected by flow cytometric cell cycle analysis and MTT cell viability analysis, and this was accompanied by dephosphorylation of the retinoblastoma protein (Rb). Furthermore, GMZ treatment resulted in increased levels of specifically the very long chain ceramides as determined by mass spectrometry. Mechanistically, GMZ did not appear to affect the activities of many enzymes of ceramide metabolism;

SUBMITTER: Wu BX 

PROVIDER: S-EPMC2788435 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature