Susceptibility to apoptosis is restored in human leukemia HCW-2 cells following induction and stabilization of the apoptotic effector Bak

Devasis Chatterjee, Panayotis Pantazis, Gang Li, Theodore A. Bremner, Eric A. Hendrickson, James H. Wyche

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3 Scopus citations

Abstract

We demonstrate that treatment of HCW-2 cells, an apoptotic resistant variant of the human HL-60 promyelocytic leukemia cell line with phorbol-12-myristate acetate (PMA), induced differentiation along the monocytic lineage. During this process there was a dramatic increase in the mitochondrial levels of the apoptosis effector, Bak, due to the stabilization of bak mRNA, which was correlated with the sensitization of HCW-2 cells to respond to the apoptotic effect of staurosporine (STS). Treatment of PMA-differentiated, but not undifferentiated, HCW-2 cells induced processing of Bid, substantial efflux of cytochrome c from mitochondria to the cytosol, activation of caspase-3 and apoptosis. The biological significance of the increased mitochondrial Bak in differentiated HCW-2 cells was supported by the finding that transient transfection of a bak cDNA into HCW-2 cells conferred sensitivity to STS-triggered apoptosis, as determined by pro-caspase-3 processing, cytochrome c efflux and DNA fragmentation. Our results suggest that the induction of Bak, upon monocytic differentiation, may be a critical event that regulates the apoptotic sensitivity of differentiated HCW-2 cells.

Original languageEnglish (US)
Pages (from-to)4108-4116
Number of pages9
JournalOncogene
Volume19
Issue number36
DOIs
StatePublished - Aug 24 2000

Bibliographical note

Funding Information:
This work was supported by a National Science Foundation grant MCB-9630362 (to JH Wyche and EA Hen-drickson). TA Bremner was supported as a Howard Hughes Visiting Professor by a grant from the Howard Hughes Medical Institute to Brown University (5-29251).

Keywords

  • Apoptosis
  • Bak
  • Differentiation
  • Leukemia cells

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