Dehydroleucodine inhibits vascular smooth muscle cell proliferation in G2 phase.
Vascular smooth muscle cell (VSMC) proliferation plays an important role in the development of atherosclerosis and in the vascular changes seen in hypertension. Dehydroleucodine (DhL) is a sesquiterpene lactone that inhibits cell proliferation in plant cells. In this paper, we study the effect of DhL in the proliferation of VSMCs stimulated with 10% fetal bovine serum (FBS). Very low concentrations of DhL (2-6 microM) inhibited VSMC proliferation and induced cell accumulation in G2. DhL did not affect the dynamics of 3H-thymidine incorporation, and did not modify either the activity of DNA polymerase or the incorporation of deoxyribonucleotides in an in vitro assay. Moreover, DhL did not induce apoptosis in VSMCs. These results indicate that DhL, in very low concentration, induces a transient arrest of VSMCs in G2. Our data show that VSMCs are especially sensitive to DhL effect, suggesting that DhL could be potentially useful to prevent the vascular pathological changes seen in hypertension and other vascular diseases.
Cruzado
M
M
Laboratorio de Cultivo de Células, Area Química Biológica-Facultad de Ciencias Médicas UNCuyo, Mendoza, Argentina.
Castro
C
C
Fernandez
D
D
Gomez
L
L
Roque
M
M
Giordano
O E
OE
Lopez
L A
LA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D003854:Deoxyribonucleotides / Q000378:metabolism; D016195:G2 Phase / Q000187:drug effects*; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects*; D016133:Polymerase Chain Reaction; D051381:Rats; D011921:Rats, Inbred WKY; D012717:Sesquiterpenes / Q000494:pharmacology*
D003854:Deoxyribonucleotides; D007783:Lactones; D012717:Sesquiterpenes; C079949:dehydroleucodine; D004247:DNA; D004259:DNA-Directed DNA Polymerase