title: 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.
authors.affiliation: Department of Orthopaedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Ya-Dong
authors.initials: YD
authors.lastname: Zheng
authors.forename: Xi-Qiang
authors.initials: XQ
authors.lastname: Xu
authors.forename: Fei
authors.initials: F
authors.lastname: Peng
authors.forename: Ji-Zhe
authors.initials: JZ
authors.lastname: Yu
authors.forename: Hua
authors.initials: H
authors.lastname: Wu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D012516:Osteosarcoma / Q000473:pathology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C025160:3-aminobenzamide; D002945:Cisplatin