Open AccessChemopreventive effect of dimethyl dicarboxylate biphenyl on malignant transformation of WB‐F344 rat liver epithelial cells 1
Author(s) -
SUN Hua,
LIU Gengtao
Publication year - 2005
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2005.00208.x
Subject(s) - in vitro , carcinogen , carcinogenesis , chemistry , malignant transformation , microbiology and biotechnology , anticarcinogen , biphenyl , downregulation and upregulation , biochemistry , cancer research , biology , biological activity , organic chemistry , gene
Aim: 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 μmol/L, 2 μmol/L, and 4 μmol/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 μmol/L and 4 μmol/L DDB. DDB at 1 μmol/L, 2 μmol/L, and 4 μmol/L inhibited the down regulation 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. Conclusion: DDB has a potential chemopreventive effect on hepatocarcinogenesis induced by carcinogens in vitro .