Inhibition of Poly(ADP-Ribose) Polymerase (PARP) Induces Apoptosis in Lung Cancer Cell Lines

Nupur N. GangopadhyayDepartment of Cardiothoracic Surgery, Department of Pathology, and University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, USACorrespondence[email protected]

James D. LuketichDepartment of Cardiothoracic Surgery, Department of Pathology, and University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, USA

Amy OpestDepartment of Cardiothoracic Surgery, Department of Pathology, and University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, USA

Carmen VisusDepartment of Cardiothoracic Surgery, Department of Pathology, and University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, USA

Ernest M. MeyerDepartment of Cardiothoracic Surgery, Department of Pathology, and University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, USA

Rodney LandreneauDepartment of Cardiothoracic Surgery, Department of Pathology, and University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, USA

Matthew J. SchuchertDepartment of Cardiothoracic Surgery, Department of Pathology, and University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, USA

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Abstract

We have tested PJ34, a potent inhibitor of poly(ADP-ribose) polymerase (PARP), against various lung cancer cell lines (Calu-6, A549, and H460) and normal human bronchial epithelial cells (HBECs). While using WST1 dye assay, lung cancer cells exhibited LD₅₀ values of approximately 30 μM PJ34 (72-hr assay). Molecular data showed that the effect of PJ34-induced apoptosis on lung cancer cells occurs via a caspase-dependent pathway. The present study has clearly shown that (a) PARP inhibitor can independently kill tumor cells, (b) caspase-3 has modest influence on PARP-inhibitor-mediated cancer-specific toxicity, and (c) a pan-caspase inhibitor decreases the apoptotic effect of PJ34.

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ACKNOWLEDGMENTS

We thank Dr. Daniel Johnson for reviewing the manuscript.

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Inhibition of Poly(ADP-Ribose) Polymerase (PARP) Induces Apoptosis in Lung Cancer Cell Lines

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Inhibition of Poly(ADP-Ribose) Polymerase (PARP) Induces Apoptosis in Lung Cancer Cell Lines

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