Induction of the mitochondrial permeability transition mediates the killing of HeLa cells by staurosporine

M. Tafani, D. A. Minchenko, A. Serroni, J. L. Farber

Research output: Contribution to journalArticle

Abstract

The role of the mitochondrial permeability transition (MPT) in the killing of HeLa cells by staurosporine (STR) was assessed with the use of bongkrekic acid (BK), an inhibitor of the MPT. BK prevented cell killing as well as biochemical manifestations of the MPT: (a) the loss of the mitochondrial membrane potential (δΨm); (b) the release of cytochrome c from the intramembranous space to the cytosol; and (c) the release of malate dehydrogenase from the mitochondrial matrix. Stable transfectants that overexpressed Akt were also resistant to cell killing and did not develop an MPT. STR inhibited the phosphorylation of Bad, whereas Bad phosphorylation was preserved in cells that overexpress Akt. In wild-type HeLa cells treated with STR, the content of Bax in the cytosol decreased as that in the mitochondria increased, a result that was again prevented by overexpression of Akt. Bid accumulation in the mitochondria with STR was not affected by overexpression of Akt. The pan-caspase inhibitor Z-Val-Ala-Val-Asp(OMe) fluoromethylketone prevented cell killing but not induction of the MPT. The data document the central role of the MPT in the killing of HeLa cells by STR. The data are consistent with the hypothesis that induction of the MPT is a consequence of the movement of Bax to the mitochondria. Phosphorylation of Bad prevents Bax translocation. Caspases participate in the events related to cell killing that occur subsequent to induction of the MPT.

Original languageEnglish
Pages (from-to)2459-2466
Number of pages8
JournalCancer Research
Volume61
Issue number6
Publication statusPublished - Mar 15 2001

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Staurosporine
HeLa Cells
Permeability
Bongkrekic Acid
Mitochondria
Phosphorylation
Cytosol
Malate Dehydrogenase
Caspase Inhibitors
Mitochondrial Membrane Potential
Caspases
Cytochromes c

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Tafani, M., Minchenko, D. A., Serroni, A., & Farber, J. L. (2001). Induction of the mitochondrial permeability transition mediates the killing of HeLa cells by staurosporine. Cancer Research, 61(6), 2459-2466.

Induction of the mitochondrial permeability transition mediates the killing of HeLa cells by staurosporine. / Tafani, M.; Minchenko, D. A.; Serroni, A.; Farber, J. L.

In: Cancer Research, Vol. 61, No. 6, 15.03.2001, p. 2459-2466.

Research output: Contribution to journalArticle

Tafani, M, Minchenko, DA, Serroni, A & Farber, JL 2001, 'Induction of the mitochondrial permeability transition mediates the killing of HeLa cells by staurosporine', Cancer Research, vol. 61, no. 6, pp. 2459-2466.
Tafani, M. ; Minchenko, D. A. ; Serroni, A. ; Farber, J. L. / Induction of the mitochondrial permeability transition mediates the killing of HeLa cells by staurosporine. In: Cancer Research. 2001 ; Vol. 61, No. 6. pp. 2459-2466.
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