title: 6-[(1-naphthylmethyl)sulfanyl]-9H-purine induces G2/M phase arrest and apoptosis in human hepatocellular carcinoma HepG2 cells.
abstract: Due to the increasing incidence of cancer, a leading cause of death worldwide, discovery of new therapeutic drugs is urgently needed. By screening for agents with low toxicity that selectively target cancer cells, we found that 6-[(1-naphthylmethyl) sulfanyl]-9H-purine (NMMP), a derivative of 6-mercaptopurine (6-MP), could reduce the viability of five human cancer cell lines. Further study suggested that NMMP inhibition of the proliferation of hepatocellular carcinoma (HepG2) cells was associated with G2/M phase cell cycle arrest, and reduced cyclin-dependent kinase (CDK) 4 and cyclin B1/D1 levels. In addition, NMMP induced cell apoptosis, as determined by TUNEL assay. Immunoblot analysis revealed that the expression of cleaved caspase-9 and caspase-3 as well as the ratio of Bax/Bcl-2 protein increased significantly. Overall, our results suggest that NMMP exerts anti-tumor activities through induction of G2/M phase arrest and mitochondria-dependent cell apoptosis, implicating its potential therapeutic value for the treatment of cancer.
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, China.
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Yang
authors.forename: Yong-Li
authors.initials: YL
authors.lastname: Bao
authors.forename: Yan-Xin
authors.initials: YX
authors.lastname: Huang
authors.forename: Lu-Guo
authors.initials: LG
authors.lastname: Sun
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Zhang
authors.forename: Chun-Lei
authors.initials: CL
authors.lastname: Yu
authors.forename: Yin
authors.initials: Y
authors.lastname: Wu
authors.forename: Yu-Xin
authors.initials: YX
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects*; D015122:Mercaptopurine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C578992:6-((1-naphthylmethyl)sulfanyl)-9H-purine; D000970:Antineoplastic Agents; D015122:Mercaptopurine