title: Diphenyl difluoroketone: a potent chemotherapy candidate for human hepatocellular carcinoma.
abstract: Diphenyl difluoroketone (EF24), a molecule having structural similarity to curcumin, was recently reported to inhibit proliferation of various cancer cells significantly. Here we try to determine the effect and mechanism of EF24 on hepatocellular carcinoma. 2 µM EF24 was found to inhibit the proliferation of PLC/PRF/5, Hep3B, HepG2, SK-HEP-1 and Huh 7 cell lines. However, even 8 µM EF24 treatment did not affect the proliferation of normal liver LO2 cells. Accordingly, 20 mg/kg/d EF24 inhibited the growth of the tumor xenografts conspicuously while causing no apparent change in liver, spleen or body weight. In addition, significant apoptosis and G(2)/M phase cell cycle arrest were found using flow cytometry. Besides, caspases and PARP activation and features typical of apoptosis including fragmented nuclei with condensed chromatin were also observed. Furthermore, the mechanism was targeted at the reduction of nuclear factor kappa b (NF-κB) pathway and the NF-κB-regulated gene products Bcl-2, COX-2, Cyclin B1. Our study has offered a strategy that EF24 being a therapeutic agent for hepatocellular carcinoma.
authors: Key Laboratory of Hepatosplenic Surgery, Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Ministry of Education, Harbin, Heilongjiang Province, People's Republic of China.
authors: Yingjian
authors: Y
authors: Liang
authors: Dalong
authors: D
authors: Yin
authors: Limin
authors: L
authors: Hou
authors: Tongsen
authors: T
authors: Zheng
authors: Jiabei
authors: J
authors: Wang
authors: Xianzhi
authors: X
authors: Meng
authors: Zhaoyang
authors: Z
authors: Lu
authors: Xuan
authors: X
authors: Song
authors: Shangha
authors: S
authors: Pan
authors: Hongchi
authors: H
authors: Jiang
authors: Lianxin
authors: L
authors: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001597:Benzylidene Compounds / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056744:Cyclin B1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D010881:Piperidones / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: C524042:3,5-bis(2-fluorobenzylidene)piperidin-4-one; D001597:Benzylidene Compounds; D056744:Cyclin B1; D016328:NF-kappa B; D010881:Piperidones; D019253:Proto-Oncogene Proteins c-bcl-2; D051546:Cyclooxygenase 2