Using a biologically annotated library to analyze the anticancer mechanism of serine palmitoyl transferase (SPT) inhibitors.

ABSTRACT: Mechanistic understanding is crucial to anticancer drug discovery. Here, we reveal that inhibition of serine palmitoyl transferase (SPT), the rate-limiting enzyme in sphingolipid synthesis, induced death in a lung cancer cell line via a necrosis-dependent pathway. To elucidate the mechanism of cell death induced by SPT inhibition, a biologically annotated library of diverse compounds was screened with an SPT inhibitor. This analysis identified suppressors of SPT inhibitor-mediated cell death. Further analysis using hit compounds from this screening revealed that SPT inhibitors induce COX-2 expression, leading to necrosis-dependent cell death. SPT inhibitors might therefore represent novel candidates for cancer therapy via necrosis pathway regulation. Our data illustrate that compound combi

SUBMITTER: Sano O 

PROVIDER: S-EPMC5377399 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature