Sulindac derivative-induced apoptosis in a human umbilical vein endothelial cell line ECV304.
OBJECTIVE
To investigate the effects of sulindac metabolites on proliferation and apoptosis in the human umbilical vein endothelial cell line ECV304 in vitro.


METHODS
The proliferation profile of ECV304 was determined by methyl thiazolyl tetrazolium (MTT) method. Cell cycle distribution, apoptosis and the ultrastructure of ECV304 were detected by flow cytometry (FCM) and electron microscopy, respectively.


RESULTS
MTT assay showed that the sulfide inhibited the proliferation of ECV304 and its effect was dose-dependent; the IC(50) was 200 micromol/L. FCM showed that the sulfide changed cell cycle distribution. The cell cycle distribution was as follows: G(1) phase (control group 77.74% +/- 1.58%; sulfone group 75.63% +/- 2.12%; sulfide group 46.12% +/- 1.60%); S phase (control group 13.64% +/- 1.22%; sulfone group 16.40 +/- 2.30%; sulfide group 27.26% +/- 2.08%); G(2)-M phase (control group 8.61% +/- 0.67%; sulfone group 7.98% +/- 0.49%; sulfide group 26.62% +/- 3.54%). The apoptosis rates in the control group, sulfone group and sulfide group were 6.08% +/- 3.39%, 4.81% +/- 2.14% and 51.90% +/- 5.67%, respectively. Sulfide reduced the proportion of G(1) phase, increased the proportion of S phase, G(2)-M phase and the apoptosis rate significantly (P < 0.01, vs control). In the sulfide-treated cells, there were nuclear fragmentation and chromosomal condensation, shrinkage of the cell and loss of contact with neighboring cells. Apoptotic bodies were observed. Sulfone showed no effect on cell proliferation, cell cycle distribution or cell morphology.


CONCLUSIONS
Sulfide can significantly reduce the proliferation of ECV304, change the cell cycle distribution and arrest cells in G(2)-M phase where apoptosis may be induced. Sulfone has no such effects on this cell line.
Liu
Suying
S
Obstetrics and Gynecologic Hospital of Fudan University, Shanghai 200011, China. Liusuying2000@yahoo.com
Feng
Youji
Y
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / 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* / Q000648:ultrastructure; D006801:Humans; D008854:Microscopy, Electron; D013467:Sulindac / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014471:Umbilical Veins
D020533:Angiogenesis Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D013467:Sulindac; C025462:sulindac sulfide; C025463:sulindac sulfone