title: Anticancer activity and mechanisms of diacetyldianhydrogalactitol on hepatoma QGY-7703 cells.
abstract: Diacetyldianhydrogalactitol (DADAG) is a member of the hexitols which shows a significant anticancer effect. Despite the fact that the antitumor effects of DADAG have been studied in a number of cell lines, the mechanism of its action remains unclear. Herein, we explored antitumor effects of DADAG and the possible mechanisms by which it inhibited the growth of human hepatocellular carcinoma cell QGY-7,703 and its derived xenograft tumors. Cell proliferation was evaluated with the sulforhodamine B assay in vitro. The results suggested that DADAG had mild antiproliferative activity on QGY-7,703 cells. The antitumor effect of DADAG was assessed in nude mice xenografted with QGY-7,703 cells. We found that DADAG significantly inhibited the tumor growth. Flow cytometry results indicated that the retarded cell proliferation is associated with increased G2/M cell cycle arrest. Further studies showed that the induced G2/M cell cycle arrest is, at least partially, attributed to an upregulation of cyclin B1, phospho-cell division cycle 2 (cdc2) (Thr), phospho-cdc2 (Thr), and cdc25c protein expression, and a decrease in cdc2 protein expression. Taken together, our data show that DADAG has mild proliferative effects on QGY-7,703 cells in vitro, but it significantly inhibits the growth of QGY-7,703 in a xenograft model in vivo. The modulation of several cell cycle progression regulation proteins responsible for G2/M phase transition may account for its antitumor effects.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing, China.
authors.forename: Xue Yan
authors.initials: XY
authors.lastname: Zhang
authors.forename: Xue
authors.initials: X
authors.lastname: Lian Yan
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jing
authors.initials: J
authors.lastname: Rong Cui
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000178:diet therapy*; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003961:Dianhydrogalactitol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy; D051379:Mice; D008819:Mice, Nude; D015854:Up-Regulation / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D003961:Dianhydrogalactitol; C027991:dianhydro-3,4-diacetylgalactitol