[Experimental study on sulindac metabolites -induced apoptosis on human umbilical vein endothelial cell line ECV304].
OBJECTIVE
To investigate the effects of sulindac metabolites on the proliferation and apoptosis of human umbilical vein endothelial cell line ECV304 in vitro.


METHODS
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.


RESULTS
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 (P < 0.01). Also sulfide induce cell apoptosis significantly (P < 0.01). 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.


CONCLUSIONS
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.
Liu
Suying
S
Department of Gynecology, Obstetric and Gynecologic Hospital, Fudan University, Shanghai 200011, China.
Feng
Youji
Y
D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D013467:Sulindac / Q000378:metabolism / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects
D000970:Antineoplastic Agents; D013467:Sulindac