[Experimental study on sulindac metabolites -induced apoptosis on human umbilical vein endothelial cell line ECV304]

To investigate the effects of sulindac metabolites on the proliferation and apoptosis of human umbilical vein endothelial cell line ECV304 in vitro.The proliferation of ECV304 was determined by methyl thiazolyl tetrazolium (MTT) method. The cell cycle, apoptosis and the ultrastructure of ECV304 were detected by flow cytometry (FCM) and electron microscopy respectively.MTT assay showed that sulfide inhibited the proliferation of ECV304, and the effects was dose-dependent, the 50% inhibiting concentration (IC(50)) was 200 micromol/L. FCM showed that sulfide changed cell cycle distribution, the cell cycle were: Go-G(1) phase [control group (77.7 +/- 1.6)%, sulfone group (75.6 +/- 2.1)%, sulfide group (46.1 +/- 1.6)%]. S phase [control group (13.6 +/- 1.2)%, sulfone group (16.4 +/- 2.3)%, sulfide group (27.3 +/- 2.1)%], G(2)-M phase [control group (8.6 +/- 0.7)%, sulfone group (8.0 +/- 0.5)%, sulfide group (26.6 +/- 3.5)%]. The apoptosis rates in control group, sulfone group and sulfide group were (6.1 +/- 3.4)%, (4.8 +/- 2.1)% and (51.9 +/- 5.7)%, respectively. Compared with the control group, sulfide can reduce the proportion of G(1) phase, increase the proportion of S phase and G(2)-M phase significantly (P0.01). Also sulfide induce cell apoptosis significantly (P0.01). In the sulfide-treated cells, chromatin concentration, cytomembrane shrinkage, neighboring cell detachment, and apaptolic body were observed. Sulfone has no effect on cell proliferation, cell cycle and cell morphology.Sulfide can reduce the viability of ECV304, change the cell cycle distribution, arrest the cell cycle in G(2)-M phase and induce apoptosis. Sulfone didnet.