Format

Send to:

Choose Destination
See comment in PubMed Commons below
Cancer Lett. 1994 May 16;79(2):147-55.

Thapsigargin-induced persistent intracellular calcium pool depletion and apoptosis in human hepatoma cells.

Author information

  • 1First Department of Medicine, University of Tokyo, Japan.

Abstract

We found that thapsigargin (Tg), a non-phorbol ester type tumor promoter that specifically inhibits endoplasmic reticulum Ca(2+)-ATPase, transiently increased the level of cytosolic free calcium ([Ca2+]i) and subsequently induced chromatin condensation, nuclear fragmentation, and internucleosomal DNA cleavage in cultured PLC/PRF/5 human hepatoma cells. These alterations were followed by the loss of plasma membrane integrity and by cell death. Epidermal growth factor (EGF) and vasopressin similarly elevated [Ca2+]i without causing DNA fragmentation which is characteristic of apoptosis. Consequently, the elevation of [Ca2+]i itself was not sufficient for causing Tg-induced cell death. On the other hand, preculturing the cells with Tg completely suppressed Ca2+ mobilization induced by EGF and vasopressin; a result that strongly suggests that Tg depleted the endoplasmic reticulum Ca2+ pool. Such depletion is hypothesized to induce apoptotic cell death in this hepatoma cell line by changing the nuclear Ca2+ levels which probably produce a structural change in chromatin.

PMID:
8019972
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Loading ...
    Write to the Help Desk