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[Cancer Research 64, 27-30, January 1, 2004]
© 2004 American Association for Cancer Research

Advances in Brief

Cathepsin B Mediates Caspase-Independent Cell Death Induced by Microtubule Stabilizing Agents in Non-Small Cell Lung Cancer Cells

Linda E. Bröker, Cynthia Huisman, Simone W. Span, José A. Rodriguez, Frank A. E. Kruyt and Giuseppe Giaccone

Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands

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.




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Copyright © 2004 by the American Association for Cancer Research.