Apoptotic Effects of Some Thiohydantoin Derivatives

Abstract

Objectives: The aim of this study is to investigate the effects of newly synthesized 3-phenly-and 3-(4-methoxyphenyl)-2-thiohydantoin derivatives on 5RP7 ve CO25 cell apoptosis. Methods and Materials: Thiohydantoin derivatives were synthesized as reported previously. The cells were grown in DMEM cell culture medium supplemented with % 10 foetal bovine serum and incubated with compounds for different time intervals. After incubation time, the effects of thiohydantoin derivatives on the viability of 5RP7 and CO25 cells determined by MTT assay. The effects of IC(50) and IC(50)/2 concentrations of compounds on cancer cell apoptosis were investigated by using acridine orange-ethidium bromide staining and annexin-V with flow cytometry analysis. Results: Thiohydantoin derivatives reduced viability of both cell lines in a time- and dose-dependent manner with their IC(50) values of 0.01-0.07 mg/ml. Both cell lines treated with 3-phenly-2-thiohydantoin derivative for 8 or 24 h exhibited the morphological changes characteristics of cell apoptosis such as chromatin condensation and apoptotic bodies. However, 3-(4-methoxyphenly)-2-thiohydantoin derivative only induced these sort of morphological changes in 5RP7 cancer cells, but not in CO25 cells. To the contrary, CO25 cells treated with either both derivatives for 24 h resulted in increment of early apoptotic cell rates as much as positive control (14.7 mg/ml etoposid). Conclusions: Both thiohydantoin derivatives were inhibited the cell viability of both 5RP7 and CO25 cells at lower doses that has showed that these newly synthesized derivatives could have anti-cancer effects. The effects of compounds on cell apoptosis have altered depending on the cell type and substituent properties of chemical structure.