Ofloxacin rhodanine derivatives induces apoptosis of human hepatocarcinoma cells / 中国药理学通报

ABSTRACT

Aim To study the effect of 6-(3-Benzyl-4-oxo-2-thioxo-thiazolidin-5-ylidenemethyl)-9-fluoro-3-methyl-10-(4-methyl-piperazin-1-yl)-2,3-dihydro-7-oxo-7-hydro-pyrido[1,2,3-de][1,4]benzoxazine (R3) on apoptosis of the human hepatocarcinoma SMMC-7721 cells (in vitro).Methods With different concentrations of R3 used to treat SMMC-7721 cells, esophageal squamous cell carcinoma EC-9706 cells, human colon adenocarcinoma cell line Caco-2 cells and in human L-02 hepatocytes (in vitro), and the inhibition effects of R3 on cell proliferation were examined by MTT assay.Cell apoptosis was determined using DAPI fluorescence staining and TUNEL method.The cell cycle was detected using flow cytometry with PI staining.Protein expression of p53 and caspase-3 was detected with Western blot analysis.Results Treatment with R3 (2~20 μmol·L-1) potently inhibited the proliferation of the cancer cells (the IC50 value at 24 h in SMMC-7721 cells, EC-9706cells and CaCO-2 cells was 3.893, 4.181 and 3.408 μmol·L-1, respectively).In contrast, R3 had weak cytotoxicity against L-02 cells with IC50 value of 38.96 μmol·L-1.Ofloxacin had weak cytotoxicity against SMMC-7721 cells with IC50 value of 240.137 μmol·L-1.Sunitinib had cytotoxicity against SMMC-7721 cells with IC50 value of 8.075 μmol·L-1.Treatment of SMMC-7721cells with different concentrations of R3 for 24 h increased the percentage of the apoptosis cells (P<0.05) and caused insufficient preparation for G1/S transition.In addition, R3 increased protein expression of p53, caspase-3 and the cleaved activated forms of caspase-3 in SMMC-7721 cells.Conclusion R3 as a kind of ofloxacin rhodanine derivatives exerts potent and selectively anticancer activity through the induction of apoptosis of SMMC-7721 cells.