Apoptosis of human hepatocellular carcinoma cells SMMC-7721 induced by C-3 methylidene thiazolidinedione acetic acid

Objective: The objective of this study was to investigate the effect of rufloxacin derivative C-3 methylidene thiazolidinedione acetic acid on apoptosis of human hepatocellular carcinoma cells SMMC-7721. Methods: Human hepatocellular carcinoma cells SMMC-7721, esophageal cancer cells EC-9706, colon cancer CaCO-2 cells, and hepatocytes L-02 were cultured in vitro with various concentrations of 6-fluoro -7-(4-methylpiperazin-1-yl)-8, 1-(sulfolatosyl)-1,4-dihydro-4-oxo-3-(3-carboxymethyl-2, 4-thiazolidinedione-5-methylidene) quinoline (R16). MTT assay was used to detect the inhibitory effect of R16 on proliferation in all cell lines. DAPI fluorescent staining and TUNEL assay were used to detect the changes of apoptosis. PI staining and flow cytometry were used to detect cell cycle changes. p53 and caspase-3 protein expression levels were detected by Western blot. Results: R16 significantly inhibited cell proliferation of SMMC-7721, EC-9706 and CaCO-2 cells under the concentration of 2-20 mu mol.L-1. The 24 hour IC50 values were 3.912, 4.215 and 3.380 mol.L-1, respectively. The 24 hour IC50 value of L-02 cells was 35.224 mu mol.L-1. The 24 hour IC50 value of rufloxacin was 226.924 mu mol.L-1 for SMMC-7721. The 24 hour IC50 value of sunitinib was 7.846 mu mol.L-1 for SMMC-7721. Following R16 treatment, cell cycle of SMMC-7721 was arrested at G1-S phase and the apoptosis rate was significantly higher compared to the control group (P< 0.05). R16 significantly increased p53 and caspase-3 expression in SMMC-7721 cells. In addition, the active fragment of caspase-3 was significantly increased. Conclusions: Rufloxacin-rhodanine derivatives exhibited a selective inhibitory effect on cancer cells and significantly induced apoptosis of human hepatocellular carcinoma cells SMMC-7721.