title: In silico identification of poly(ADP-ribose)polymerase-1 inhibitors and their chemosensitizing effects against cisplatin-resistant human gastric cancer cells.
abstract: Poly(ADP-ribose)polymerase-1 (PARP-1) enzyme is involved in the repair of DNA damages made by certain anticancer agents. It is suggested that PARP-1 inhibitors potentiate the cytotoxic effects and circumvent the resistance of DNA-modifying anticancer agents such as cisplatin. In this study, we conducted virtual screening of Korea Chemical Bank database targeting PARP-1 and identified several potent PARP-1 inhibitors with submicromolar IC50 values (77-79 nM). We then examined the chemosensitization of cisplatin by pre-treatment of PARP-1 inhibitors in cisplatin-resistant human gastric cancer cells. Our results show that PARP-1 inhibitors suppress the formation of poly(ADP-ribose) and enhance the cytotoxicity of cisplatin.
authors.affiliation: School of Pharmacy, Sungkyunkwan [corrected] University, Suwon 440-746, Republic of Korea.
authors.forename: Tuong Vy Thi
authors.initials: TV
authors.lastname: Le
authors.forename: Jee Hee
authors.initials: JH
authors.lastname: Suh
authors.forename: Nakjeong
authors.initials: N
authors.lastname: Kim
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Park
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D001665:Binding Sites; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use; D016208:Databases, Factual; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D062105:Molecular Docking Simulation; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000201:enzymology
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases; D002945:Cisplatin