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Involvement of Bcl-2 cleavage in the acceleration of VP-16-induced U937 cell apoptosis

N Fujita1, T Tsuruo

  • 1Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.

Biochemical and Biophysical Research Communications
|June 4, 1998
PubMed

Insights

Anticancer drug VP-16 induces apoptosis by cleaving the Bcl-2 protein in U937 cells. This cleavage, mediated by caspase-3/CPP32, promotes cell death, enhancing VP-16

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Apoptosis, or programmed cell death, is crucial for tissue homeostasis and eliminating damaged cells.
  • The Bcl-2 protein typically suppresses apoptosis, but its cleavage is linked to various apoptotic pathways.
  • Previous studies indicated Bcl-2 cleavage during apoptosis induced by Fas ligation, IL-3 withdrawal, and viral infections.

Purpose of the Study:

  • To investigate whether Bcl-2 protein is cleaved during anticancer drug VP-16-induced apoptosis in U937 cells.
  • To identify the specific protease responsible for Bcl-2 cleavage in this context.
  • To determine the functional consequence of Bcl-2 cleavage on VP-16-induced apoptosis.

Main Methods:

  • Treatment of U937 cells with the anticancer drug VP-16.
  • Analysis of Bcl-2 protein cleavage in vivo and in vitro.
  • Assessment of caspase-3/CPP32 activation following VP-16 treatment.
  • Overexpression studies of cleaved Bcl-2 fragments.

Main Results:

  • VP-16 treatment led to the cleavage of Bcl-2 protein in U937 cells, both in vivo and in vitro.
  • Caspase-3/CPP32 was activated by VP-16 and directly cleaved the Bcl-2 protein.
  • Overexpression of the cleaved Bcl-2 fragment enhanced U937 cell sensitivity to VP-16 and promoted apoptosis.

Conclusions:

  • Caspase-3/CPP32 accelerates VP-16-induced apoptosis in U937 cells.
  • This acceleration occurs through the direct cleavage of the death suppressor Bcl-2 protein.
  • Cleavage generates a Bcl-2 fragment that promotes cell death, thus contributing to the drug's efficacy.

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