PARP inhibitor activates the intrinsic pathway of apoptosis in primary lung cancer cells.

This investigation was aimed to see whether PJ34(TM), a PARP inhibitor, could exert cytotoxicity in six nonsmall cell lung cancer cell lines developed from surgically resected tissues. Using various biochemical assays, we have seen that PJ34(TM) effects are consistent between untreated and treated samples but still somewhat variable between each cell line. Changes in protein expression and mitochondrial membrane potential between treated and untreated cells were indicating the possibility of apoptosis induction through an intrinsic pathway which causes cytotoxicity. Present results open the possibility of elucidating a decisive mechanism and effectiveness of chemotherapeutics specific to a patient.

Inhibition of poly(ADP-ribose) polymerase (PARP) induces apoptosis in lung cancer cell lines.

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 LD(50) 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.