Chemopreventive effect of dimethyl dicarboxylate biphenyl on malignant transformation of WB-F344 rat liver epithelial cells.
OBJECTIVE
To study the potential chemopreventive effect of dimethyl dicarboxylate biphenyl (DDB), an anti-hepatitis drug, on hepatocarcinogenesis in vitro.


METHODS
The anti-carcinogenesis effect of DDB was assessed on a two-stage chemical oncogenesis model induced by 3-methylcholanthrene and 12-O-tetradecanoyl phorbol 13-acetate (TPA) with WB-F344 rat liver epithelial cells (WB-F344 cells) in vitro. A soft-agar colony formation assay was used to determine the tumorigenic potential of the transformed WB-F344 cells. The gap junctional intercellular communication (GJIC) was detected using the scrape loading/dye transfer technique.


RESULTS
DDB at 1 micromol/L, 2 micromol/L, and 4 micromol/L significantly prevented the malignant transformation of WB-F344 cells induced by 3-methylcholanthrene and TPA. The average number of transformed foci decreased dramatically by 10.0%, 37.2%, and 47.4%, respectively. In soft agar, a remarkable decrease in colony numbers was observed in transformed cells treated with 2 micromol/L and 4 micromol/L DDB. DDB at 1 micromol/L, 2 micromol/L, and 4 micromol/L inhibited the downregulation of GJIC induced by TPA in a dose-dependent manner. The GJIC recovered to 25.6%, 34.6%, and 44.9%, respectively, of the control WB-F344 cells by DDB.


CONCLUSIONS
DDB has a potential chemopreventive effect on hepato-carcinogenesis induced by carcinogens in vitro.
Sun
Hua
H
Department of Pharmacology, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China.
Liu
Geng-tao
GT
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002273:Carcinogens; D002450:Cell Communication / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000187:drug effects*; D002478:Cells, Cultured; D004149:Dioxoles / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D017629:Gap Junctions / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D013755:Tetradecanoylphorbol Acetate
D000970:Antineoplastic Agents; D002273:Carcinogens; D004149:Dioxoles; D004365:Drugs, Chinese Herbal; C041398:7,7'-dimethoxy-(4,4'-bi-1,3-benzodioxole)-5,5'-dicarboxylic acid dimethyl ester; D013755:Tetradecanoylphorbol Acetate