title: 3-Bromopyruvic acid, a hexokinase II inhibitor, is an effective antitumor agent on the hepatoma cells : in vitro and in vivo findings.
abstract: Over-expressed in cancer cells, hexokinase II (HK II) forms a mitochondrial complex, which promotes cancer survival. 3- Bromopyruvic acid (3-BrPA) dissociates HK II from this complex, causing cell death, and thus, having an anti-tumor effect. The design of this study was to first analyze the expression of HK II in the hepatoma cell line, BEL-7402, then investigate the effects of 3-Br-PA on these cells, and finally, discuss its potential for clinical usage. HK II expression was detected in BEL-7402 cells by immunocytochemistry and reverse transcriptase polymerase chain reaction (RT-PCR). In vitro treatment of cells with 3-BrPA significantly inhibited their growth, as evaluated by MTT assay and adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA). To analyze the in vivo function and safety of this drug, a tumor model was established by subcutaneously implanting hepatic cancer cells into nude mice. 3-BrPA treatment (50 mg/kg ip. daily, 6 days/week for three weeks) was effective in the animal model by attenuating tumor growth and causing tumor necrosis. Toxic signs were not observed. The acute toxicity study provided an LD50 of 191.7 mg/kg for 3-BrPA. Taken together, our in vitro and in vivo analyses suggest that 3-BrPA exerts anti-hepatoma effects, and may be an effective pharmacological agent for the treatment of hepatocellular carcinoma.
authors.forename: Lei
authors.initials: L
authors.lastname: Gong
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Wei
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.forename: Jirun
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Hepatobiliary Surgery, Peking University People's Hospital, No.11 South Xizhimen Street, Xicheng District, Beijing 100044, PR China. jrpeng2010@126.com.
authors.forename: Xisheng
authors.initials: X
authors.lastname: Leng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006593:Hexokinase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007928:Lethal Dose 50; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009336:Necrosis; D011773:Pyruvates / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D011773:Pyruvates; C017092:bromopyruvate; D006593:Hexokinase