Cathepsin B mediates caspase-independent cell death induced by microtubule stabilizing agents in non-small cell lung cancer cells. Academic Article uri icon

Overview

abstract

  • We have previously reported that the microtubule stabilizing agents (MSAs) paclitaxel, epothilone B and discodermolide induce caspase-independent cell death in non-small cell lung cancer (NSCLC) cells. Here we present two lines of evidence indicating a central role for the lysosomal protease cathepsin B in mediating cell death. First, inhibition of cathepsin B, and not of caspases or other proteases, such as cathepsin D or calpains, results in a strong protection against drug-induced cell death in several NSCLC cells. Second, MSAs trigger disruption of lysosomes and release and activation of cathepsin B. Interestingly, inhibition of cathepsin B prevents the appearance of multinucleated cells, an early characteristic of MSA-induced cell death, pointing to a central, proximal role for cathepsin B in this novel cell death pathway.

publication date

  • January 1, 2004

Research

keywords

  • Antineoplastic Agents
  • Apoptosis
  • Caspases
  • Cathepsin B
  • Microtubules
  • Paclitaxel

Identity

Scopus Document Identifier

  • 1642576236

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.can-03-3060

PubMed ID

  • 14729603

Additional Document Info

volume

  • 64

issue

  • 1