Differential Regulation of Specific Sphingolipids in Colon Cancer Cells during Staurosporine-Induced Apoptosis

Chem Biol. 2015 Dec 17;22(12):1662-70. doi: 10.1016/j.chembiol.2015.11.004.

Abstract

Apoptosis is accompanied by distinct morphological changes at the plasma and organelle membrane level. Involvement of certain lipids in apoptosis has been established; however, we have limited understanding of the specific lipid structures that participate in this process. We used untargeted comparative lipidomics to study the changes in lipid composition during staurosporine-induced apoptosis in HCT-116. Our results revealed that ceramides, dihydroceramides, and sphingomyelins, with defined acyl chains, constitute the majority of changes in the lipidome. Expression levels and activities of enzymes responsible for the biosynthesis of lipids that change suggest that de novo synthesis causes these specific changes. Further analysis of the lipidome during apoptosis in other cancer and non-cancer cell lines suggested that accumulation of ceramides and dihydroceramides is specific to cancer cells. Taken together, our data propose that these molecules are regulated at the lipid-specific level during apoptosis and that this regulation differs between cancer and non-cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / physiology*
  • Cell Survival
  • Colonic Neoplasms / drug therapy
  • HCT116 Cells
  • Humans
  • Mass Spectrometry
  • Molecular Structure
  • Polymerase Chain Reaction
  • Sphingolipids / analysis
  • Sphingolipids / metabolism*
  • Staurosporine / pharmacology*

Substances

  • Sphingolipids
  • Staurosporine