According to epidemiological studies, dietary intake of cruciferous vegetables may be protective against the risk of cancer. Isothiocyanates (ITCs) are found in cruciferous vegetables, including broccoli, cabbage, watercress and cauliflower. Recent studies had been shown that ITCs are classes of naturally occurring chemopreventive and possibly chemotherapeutic agents. Phenethyl isothiocyanate (PEITC) is one of the most common researched ITCs. The recent studies reported that PEITC can induce cancer cell growth inhibition or apoptosis of human prostate, leukemia and hepatoma cancer cells. However, the molecular mechanism and signaling pathway of PEITC-induced apoptosis in human malignant melanoma A375.S2 cells are still not clear. In this study, apoptosis induced by PEITC in A375.S2 cells was investigated. PEITC induced cell death in time- and dose-dependent manners was found in MTT assay. Cell cycle analysis, reactive oxygen species (ROS) generation, intercellular Ca2+ detection, the change of level mitochondria membrane potential (ΔΨm) and caspase-3 activity in A375.S2 cells were detected by flow cytometry after exposure to PEITC. Chromatin condensation and DNA damage were determined by DAPI staining, Comet assay and DNA gel electrophoresis. The results showed that PEITC caused chromatin condensation, DNA damage, cell cycle G2/M phase arrest, promoted ROS generation, stimulated Ca2+ release, loss of ΔΨm and activated caspase-3 activity lead to cell apoptosis in human malignant melanoma A375.S2 cells.
PEITC Induces Apoptosis in Human Malignant Melanoma A375.S2 Cells through Reactive Oxygen Species and Mitochondria-dependent Pathways
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