Thalidomide and a thalidomide analogue inhibit endothelial cell proliferation in vitro.
Angiogenesis is a crucial process in inflammatory reactions as well as in tumor implantation and growth. Tumors with high rates of invasion and recurrence such as gliomas, are specially dependent on neovascularization. This suggests that inhibition of angiogenesis might reduce the growth of these tumors. Thalidomide has been previously shown to inhibit angiogenesis induced by basic fibroblast growth factor in vivo, using the rabbit corneal micropocket assay. Therefore, the effect of thalidomide and a thalidomide analogue (cc-1069) on the proliferation in vitro of endothelial and glioma cells was tested. We observed a decrease in endothelial cell proliferation in cultures treated with thalidomide or the thalidomide analogue cc-1069. The analogue inhibited endothelial cell proliferation more efficiently than thalidomide. The inhibition occurred in association with a marked decrease in the activity of the nuclear factor SP1 and a moderate inhibition of NF-kappaB activation in nuclear extracts of endothelial cells. The drugs did not impair cell viability. There was no effect of thalidomide or the thalidomide analogue on the proliferation of the glioma cell line (U251) in vitro.
Moreira
A L
AL
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY, USA.
Friedlander
D R
DR
Shif
B
B
Kaplan
G
G
Zagzag
D
D
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003315:Cornea / Q000098:blood supply; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005910:Glioma; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D011817:Rabbits; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014471:Umbilical Veins
D016328:NF-kappa B; D016329:Sp1 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D013792:Thalidomide