The poly(ADP-ribose) polymerase-1 inhibitor 3-aminobenzamide suppresses cell growth and migration, enhancing suppressive effects of cisplatin in osteosarcoma cells

Abstract

Pharmacological inhibition of DNA repair pathways has been emerging as an effective tool for cancer treatment. Poly(ADP-ribose) polymerase (PARP) is involved in DNA repair and transcriptional regulation and is now recognized as a key regulator of cell survival and cell death. In vitro and in vivo data suggest that PARP inhibitors could be used not only as chemo/radiotherapy sensitizers but also as single agents to selectively kill cancer cells in certain types of tumors. In the present study, we investigate the effects of 3-aminobenzamide (3-AB), a potent inhibitor of PARP, on human osteosarcoma cells and whether or not it can sensitize the tumor cells to chemotherapeutic agents. The results indicated that 3-AB suppressed U2OS cell growth in a time- and dose-dependent manner, and the suppressive effects of 3-AB were associated with increased cell apoptosis. In addition, 3-AB suppressed cell invasion in vitro and enhanced the suppressive effects of cisplatin in U2OS cells. Our work suggests that this PARP-1 inhibitor may be developed into an effective agent for the treatment of human osteosarcoma.