Imidazole-thiazolidinone inhibits oesophageal cancer cell proliferation via induction of apoptosis and cell cycle arrest at S phase

Abstract

Purpose: To investigate the effect of imidazole-thiazolidinone on oesophageal cancer (OC) cell proliferation, and the mechanism of action involved.Methods: Human OC cells (HCE-6 and KYSE-1170) were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10 % fetal bovine serum (FBS) and 1 % penicillin/streptomycin solution at 37 ˚C for 24 h in a humidified atmosphere of 5 % CO2 and 95 % air. After attaining 60 -  70 % confluency, the cells were treated with serum-free medium and graded concentrations of imidazolethiazolidinone (up to 160 μM) for 24 h. Normal cell culture without imidazole-thiazolidinone served as control. Cells in logarithmic growth phase were selected and used in this study. Cell proliferation and apoptosis were assessed using 3 (4,5 dimethyl thiazol 2 yl) 2,5 diphenyl 2H tetrazolium bromide (MTT), and flow cytometric assays, respectively. The levels of expression of apoptosis-related proteins were determined using Western blotting.Results: Treatment of HCE-6 and KYSE-1170 cells with imidazole-thiazolidinone for 48 h led to significant and dose-dependent reduction in their  proliferation, as well as significant and dosedependent increase in the number of apoptotic cells (p < 0.05). Light microscopy revealed significantreduction in HCE-6 cell count, detached cells, reduced cell size and irregular cytoplasmic vacuoles. Imidazole-thiazolidinone treatment significantly and dose-dependently decreased HCE-6 and KYSE-1170 cell migration, and arrested HCE-6 cell cycle at S phase (p < 0.05). In HCE-6 cells, imidazolethiazolidinone treatment significantly and dose-dependently upregulated the expressions of cleaved caspase-3/8/9 and bax, but down-regulated bcl-2 expression significantly and dose-dependently (p < 0.05). However, metalloproteinases 2 and 9 (MMP-2 and MMP-9) expressions in HCE-6 and KYSE-1170 cells were significantly and dose-dependently down-regulated by imidazole-thiazolidinone treatment (p < 0.05).Conclusion: The results obtained in this study suggest that imidazole-thiazolidinone suppresses OC cell proliferation via induction of apoptosis and arrest of cell cycle at S phase. Keywords: Imidazole-thiazolidinone, Oesophageal cancer, Metastasis, Cell cycle arrest, Apoptosis