title: PJ34, an inhibitor of PARP-1, suppresses cell growth and enhances the suppressive effects of cisplatin in liver cancer cells.
abstract: It has been suggested that poly(ADP-ribose) polymerase-l (PARP-l) plays an important role in DNA repair, cell death and proliferation, as well as in the stabilization of the genome. Pharmacological inhibition or genetic ablation of PARP-1 had a beneficial outcome in cancer chemotherapy since the cancer cells lacked PARP-1 and were sensitive to chemotherapeutic DNA damage. As a novel potent specific inhibitor of PARP-l, PJ34 has been reported to enhance chemotherapeutic effects in certain types of tumors. In a previous study, we found that PARP-1 expression was significantly increased in human hepatocellular carcinoma (HCC) compared to its surrounding liver tissue. This study investigated whether or not the inhibition of PARP-1 activity by PJ34 produces suppressive effects on human liver cancer cells and sensitizes the tumor cells to chemotherapeutic agents. We conclude that PJ34 significantly suppresses HepG2 cell growth in a dose-dependent manner, and inhibits HepG2 cell-derived tumor growth in nude mice. The suppressive effects of PJ34 are associated with increased cell apoptosis. Furthermore, PJ34 enhances suppressive effects of cisplatin in HepG2 cells. These results suggest that PJ34 may be developed into an effective agent for the treatment of human HCC.
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China.
authors.forename: Sheng-Hui
authors.initials: SH
authors.lastname: Huang
authors.forename: Min
authors.initials: M
authors.lastname: Xiong
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Chen
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Xiao
authors.forename: Yin-Feng
authors.initials: YF
authors.lastname: Zhao
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Huang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010616:Phenanthrenes / Q000627:therapeutic use*; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C434926:N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; D010616:Phenanthrenes; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D002945:Cisplatin