Bcl-2 protects against beta-lapachone-mediated caspase 3 activation and apoptosis in human myeloid leukemia (HL-60) cells.

S. M. Planchon, S. M. Wuerzberger-Davis, J. J. Pink, Kent Robertson, W. G. Bornmann, D. A. Boothman

Research output: Contribution to journalArticle

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Abstract

We previously demonstrated that beta-lapachone (beta-lap) killed cancer cells solely by apoptosis. Beta-Lap induced apoptosis in HL-60 cells in a dose-dependent manner as measured by flow cytometry and DNA ladder formation. Cell cycle changes, such as accumulations in S and G2-phases, were not observed. Apoptosis was accompanied by activation of caspase 3 and concomitant cleavage of poly(ADP-ribose) polymerase (PARP) to an 89 kDa polypeptide. PARP cleavage was blocked by zDEVD-fmk or zVAD-fmk, caspase-specific cleavage site inhibitors. Retrovirally introduced bcl-2 prevented beta-lap-mediated caspase 3 activation and PARP cleavage and increased the viability of Bcl-2-expressing HL-60 cells compared to cells with vector alone. Various beta-lap-related analogs (e.g., dunnione and naphthoquinone derivatives) induced equivalent apoptosis in HL-60 cells, but no compound was more effective than beta-lap. These data provide further evidence that the primary mode of cell killing by beta-lap is by the initiation and execution of apoptosis in human cancer cells.

Original languageEnglish (US)
Pages (from-to)485-492
Number of pages8
JournalOncology Reports
Volume6
Issue number3
StatePublished - May 1999
Externally publishedYes

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Myeloid Leukemia
HL-60 Cells
Caspase 3
Poly(ADP-ribose) Polymerases
Apoptosis
Naphthoquinones
G2 Phase
Caspases
S Phase
Neoplasms
Cell Cycle
Flow Cytometry
beta-lapachone
Peptides
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Planchon, S. M., Wuerzberger-Davis, S. M., Pink, J. J., Robertson, K., Bornmann, W. G., & Boothman, D. A. (1999). Bcl-2 protects against beta-lapachone-mediated caspase 3 activation and apoptosis in human myeloid leukemia (HL-60) cells. Oncology Reports, 6(3), 485-492.

Bcl-2 protects against beta-lapachone-mediated caspase 3 activation and apoptosis in human myeloid leukemia (HL-60) cells. / Planchon, S. M.; Wuerzberger-Davis, S. M.; Pink, J. J.; Robertson, Kent; Bornmann, W. G.; Boothman, D. A.

In: Oncology Reports, Vol. 6, No. 3, 05.1999, p. 485-492.

Research output: Contribution to journalArticle

Planchon, SM, Wuerzberger-Davis, SM, Pink, JJ, Robertson, K, Bornmann, WG & Boothman, DA 1999, 'Bcl-2 protects against beta-lapachone-mediated caspase 3 activation and apoptosis in human myeloid leukemia (HL-60) cells.', Oncology Reports, vol. 6, no. 3, pp. 485-492.
Planchon, S. M. ; Wuerzberger-Davis, S. M. ; Pink, J. J. ; Robertson, Kent ; Bornmann, W. G. ; Boothman, D. A. / Bcl-2 protects against beta-lapachone-mediated caspase 3 activation and apoptosis in human myeloid leukemia (HL-60) cells. In: Oncology Reports. 1999 ; Vol. 6, No. 3. pp. 485-492.
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