PMID- 9294614
OWN - NLM
STAT- MEDLINE
DCOM- 19971002
LR  - 20071114
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 15
IP  - 10
DP  - 1997 Sep 4
TI  - Baculovirus p35 and Z-VAD-fmk inhibit thapsigargin-induced apoptosis of breast 
      cancer cells.
PG  - 1207-12
AB  - Programmed cell death, or apoptosis, is inhibited by the antiapoptotic oncogene, 
      Bcl-2, and is mediated by a cascade of aspartate-specific cysteine proteases, or 
      caspases, related to interleukin 1-beta converting enzyme. Depending on cell 
      type, apoptosis can be induced by treatment with thapsigargin (TG); a selective 
      inhibitor of the endoplasmic reticulum-associated calcium-ATPase. The role of 
      caspases in mediating TG-induced apoptosis was investigated in the Bcl-2-negative 
      human breast cancer cell line, MDA-MB-468. Apoptosis developed in MDA-MB-468 
      cells over a period of 24-72 h following treatment with 100 nM TG, and was 
      prevented by Bcl-2 overexpression. TG-induced apoptosis was associated with 
      activation of caspase-3 and was inhibited by stable expression of the baculovirus 
      p35 protein, an inhibitor of caspase activity. Also, TG-induced apoptosis was 
      inhibited by treating cells with Z-VAD-fmk, a cell-permeable fluoromethylketone 
      inhibitor of caspases. These findings indicate that TG-induced apoptosis of 
      MDA-MB-468 breast cancer cells is subject to inhibition by Bcl-2 and is mediated 
      by caspase activity. This model system should be useful for further investigation 
      directed toward understanding the role of calcium in signaling apoptosis, and its 
      relationship to Bcl-2 and the caspase proteolytic cascade.
FAU - Qi, X M
AU  - Qi XM
AD  - Department of Medicine, Case Western Reserve University/Ireland Cancer Center, 
      Cleveland, Ohio 44106, USA.
FAU - He, H
AU  - He H
FAU - Zhong, H
AU  - Zhong H
FAU - Distelhorst, C W
AU  - Distelhorst CW
LA  - eng
GR  - R21 CA/AG66221/CA/NCI NIH HHS/United States
GR  - T32 CA59366/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Amino Acid Chloromethyl Ketones)
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - 0 (Inhibitor of Apoptosis Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Viral Proteins)
RN  - 0 (benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone)
RN  - 0 (inhibitor of apoptosis, Nucleopolyhedrovirus)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
SB  - IM
MH  - Amino Acid Chloromethyl Ketones/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Breast Neoplasms/*pathology
MH  - Caspase 3
MH  - *Caspases
MH  - Cysteine Endopeptidases/metabolism/*physiology
MH  - Cysteine Proteinase Inhibitors/*pharmacology
MH  - Enzyme Activation
MH  - Humans
MH  - Inhibitor of Apoptosis Proteins
MH  - Proto-Oncogene Proteins c-bcl-2/*physiology
MH  - Signal Transduction
MH  - Thapsigargin/*pharmacology
MH  - Tumor Cells, Cultured
MH  - Viral Proteins/*pharmacology
EDAT- 1997/09/19 00:00
MHDA- 1997/09/19 00:01
CRDT- 1997/09/19 00:00
PHST- 1997/09/19 00:00 [pubmed]
PHST- 1997/09/19 00:01 [medline]
PHST- 1997/09/19 00:00 [entrez]
AID - 10.1038/sj.onc.1201290 [doi]
PST - ppublish
SO  - Oncogene. 1997 Sep 4;15(10):1207-12. doi: 10.1038/sj.onc.1201290.