Gemcitabine kills proliferating endothelial cells exclusively via acid sphingomyelinase activation.

ABSTRACT: Gemcitabine is a widely-used anti-cancer drug with a well-defined mechanism of action in normal and transformed epithelial cells. However, its effect on endothelial cells is largely unknown. Acid sphingomyelinase (ASMase) is highly expressed in endothelial cells, converting plasma membrane sphingomyelin to pro-apoptotic ceramide upon activation by diverse stresses. In the current study, we investigated gemcitabine impact in primary cultures of endothelial cells. We find baseline ASMase increases markedly in bovine aortic endothelial cells (BAEC) as they transit from a proliferative to a confluent growth-arrested state. Further, gemcitabine activates ASMase and induces release of a secretory ASMase form into the media only in proliferating endothelial cells. Additionally, proliferative, but

SUBMITTER: van Hell AJ 

PROVIDER: S-EPMC5565230 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature