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Updated: Aug 14, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles
Published on: October 5, 2012
Bcl-2 protects against beta-lapachone-mediated caspase 3 activation and apoptosis in human myeloid leukemia (HL-60)
S M Planchon1, S M Wuerzberger-Davis, J J Pink
1Department of Radiation Oncology, Laboratory of Molecular Stress Responses, Case Western Reserve University, Cleveland, OH 44106, USA.
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.
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