PRECLINICAL REPORTSAnticancer activity and mechanisms of diacetyldianhydrogalactitol on hepatoma QGY-7703 cellsZhang, Xue Yan; Lian Yan, Xue; Guo, Wei; Xu, Bo; Li, Min; Zhou, Ying; Rong Cui, JingAuthor Information State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing, China Correspondence to Professor Jing Rong Cui, MD, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China Tel: +86 10 8280 2467; fax: +86 10 8280 2467; e-mail: [email protected] Received 15 March 2009 Revised form accepted 13 July 2009 Anti-Cancer Drugs: November 2009 - Volume 20 - Issue 10 - p 926-931 doi: 10.1097/CAD.0b013e328330c7b9 Buy Metrics 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-7703 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-7703 cells. The antitumor effect of DADAG was assessed in nude mice xenografted with QGY-7703 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) (Thr15), phospho-cdc2 (Thr161), and cdc25c protein expression, and a decrease in cdc2 protein expression. Taken together, our data show that DADAG has mild proliferative effects on QGY-7703 cells in vitro, but it significantly inhibits the growth of QGY-7703 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. © 2009 Lippincott Williams & Wilkins, Inc.