[Antiangiogenic activity of thalidomide in vitro mediated by cytochrome CYP2C19].
This study was aimed to investigate the effect of metabolic system in human hepatic cell microsome on antiangiogenic in vitro activity of thalidomide used in treating multiple myeloma and to explore the role of cytochrome CYP2C19. Human umbilical cord vein endothelial cells (hUCVECs) were treated with thalidomide alone or thalidomide co-incubated with human hepatic cell microsome. Cell proliferation ability was assessed by MTT assay, cell cycle analysis and detection of apoptosis were carried out by flow cytometry (FCM), migration activity of hUCVECs was determined by modified Boyden chamber and differentiation of hUCVECs was assayed by tube formation test. The results showed that thalidomide alone had no obvious direct effect on hUCVEC viability or apoptosis, mild effect on cell migration and no effect on tube formation. However, when co-incubated with human hepatic cell microsome, thalidomide significantly inhibited the hUCVECs viability. At 100 microg/ml, thalidomide co-incubated with human hepatic cell microsome, the proliferation ability of hUCVECs decreased by (11.7 +/- 3.9)%, apoptosis cells increased by 27.2%, the cell migration was down-regulated significantly, and the tube formation was obviously inhibited. When omeprazole, a specific inhibitor of cytochrome CYP2C19, was added into the co-incubation mixture, the effects of thalidomide on cell proliferation ability, apoptosis, migration and tube formation decreased. It is concluded that effect of human hepatic cell microsome is required for thalidomide's antiangiogenic activity in vitro and cytochrome CYP2C19 may be involved in the antiangiogenic effect of thalidomide.
Li
Yong-Hua
YH
Department of Hematology, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, China.
Hou
Jian
J
Jiang
Hua
H
Huang
Hong-Ming
HM
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001189:Aryl Hydrocarbon Hydroxylases / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D065731:Cytochrome P-450 CYP2C19; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009101:Multiple Myeloma; D013792:Thalidomide / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology
D020533:Angiogenesis Inhibitors; D013792:Thalidomide; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19