Lactacystin augments the sulindac-induced apoptosis in HT-29 cells

Apoptosis. 2003 Jun;8(3):301-5. doi: 10.1023/a:1023681007766.

Abstract

The present study was conducted to explore the potential role of proteasome pathway in NSAIDs-induced apoptosis. We employed sulindac as a NSAID, and chose the lactacystin for inhibition of proteasome activity. Assessment of apoptosis and proteasome activity assay were undertaken. We demonstrated that sulindac treatment resulted in a decrease of proteasome activity, and that the co-treatment of a proteasome inhibitor lactacystin potentiated the extent of sulindac-induced apoptosis in HT-29 cells by augmentation of the decrease in proteasome activity. Elucidation of the mechanism underlying the regression of colon cancers by combinations of sulindac and lactacystin seems to be an immediate challenge for the near future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / analogs & derivatives*
  • Acetylcysteine / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Carcinoma / drug therapy
  • Carcinoma / enzymology
  • Cell Line, Tumor
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / enzymology
  • Cysteine Endopeptidases / metabolism
  • Cysteine Proteinase Inhibitors / pharmacology
  • Drug Synergism
  • HT29 Cells
  • Humans
  • Multienzyme Complexes / antagonists & inhibitors*
  • Multienzyme Complexes / metabolism
  • Proteasome Endopeptidase Complex
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Sulindac / pharmacology*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cysteine Proteinase Inhibitors
  • Multienzyme Complexes
  • lactacystin
  • Sulindac
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • Acetylcysteine