PMID- 14729603
OWN - NLM
STAT- MEDLINE
DCOM- 20040401
LR  - 20191108
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 64
IP  - 1
DP  - 2004 Jan 1
TI  - Cathepsin B mediates caspase-independent cell death induced by microtubule 
      stabilizing agents in non-small cell lung cancer cells.
PG  - 27-30
AB  - 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.
FAU - Broker, Linda E
AU  - Broker LE
AD  - Department of Medical Oncology, VU University Medical Center, Amsterdam, the 
      Netherlands.
FAU - Huisman, Cynthia
AU  - Huisman C
FAU - Span, Simone W
AU  - Span SW
FAU - Rodriguez, Jose A
AU  - Rodriguez JA
FAU - Kruyt, Frank A E
AU  - Kruyt FA
FAU - Giaccone, Giuseppe
AU  - Giaccone G
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Alkanes)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Carbamates)
RN  - 0 (DNA Primers)
RN  - 0 (Epothilones)
RN  - 0 (Lactones)
RN  - 0 (Pyrones)
RN  - DHG59994DN (discodermolide)
RN  - EC 3.4.22.- (Caspases)
RN  - EC 3.4.22.1 (Cathepsin B)
RN  - P88XT4IS4D (Paclitaxel)
RN  - UEC0H0URSE (epothilone B)
SB  - IM
MH  - Alkanes/toxicity
MH  - Antineoplastic Agents/*toxicity
MH  - Apoptosis/*drug effects
MH  - Base Sequence
MH  - Carbamates/toxicity
MH  - Carcinoma, Non-Small-Cell Lung
MH  - Caspases/*metabolism
MH  - Cathepsin B/*metabolism
MH  - Cell Death
MH  - DNA Primers
MH  - Epothilones/toxicity
MH  - Humans
MH  - Lactones/toxicity
MH  - Lung Neoplasms
MH  - Lysosomes/drug effects/enzymology
MH  - Microscopy, Fluorescence
MH  - Microtubules/drug effects/*physiology
MH  - Paclitaxel/*toxicity
MH  - Pyrones
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 2004/01/20 05:00
MHDA- 2004/04/02 05:00
CRDT- 2004/01/20 05:00
PHST- 2004/01/20 05:00 [pubmed]
PHST- 2004/04/02 05:00 [medline]
PHST- 2004/01/20 05:00 [entrez]
AID - 10.1158/0008-5472.can-03-3060 [doi]
PST - ppublish
SO  - Cancer Res. 2004 Jan 1;64(1):27-30. doi: 10.1158/0008-5472.can-03-3060.