Garlic components inhibit angiotensin II-induced cell-cycle progression and migration: Involvement of cell-cycle inhibitor p27(Kip1) and mitogen-activated protein kinase.
Garlic has been used for prevention and treatment of hypertension; however, the molecular mechanisms of garlic's effects remain to be elucidated. In this study, the mechanisms of the in vitro effect of organosulphur compounds derived from garlic on growth and migration of cultured aortic smooth muscle cells isolated from spontaneously hypertensive rats were investigated. We demonstrated that allyl methyl sulphide (AMS) and diallyl sulphide (DAS) inhibited aortic smooth muscle cell angiotensin II-stimulated cell-cycle progression and migration. Neither cell viability nor annexin-V-binding analysis revealed cytotoxic effects of both organosulphur compounds at the used concentrations. Instead, their inhibitory effects were associated to the prevention of the cell-cycle inhibitor p27(Kip1) (p27) downregulation and the reduction of extracellular signal-regulated kinase 1/2 phosphorylation. When we assessed the antioxidant activity of AMS and DAS, we found that both organosulphur compounds inhibited angiotensin II-reactive oxygen species generation. Our findings show that AMS and DAS, compounds derivate from garlic, could be effective antioxidants targeted at the arterial remodelling seen in hypertension.
Castro
Claudia
C
Laboratory of Vascular Biology, IMBECU-CONICET, Avda. Libertador 80, Mendoza, Argentina. ccastro@fcm.uncu.edu.ar
Lorenzo
Andrea Gil
AG
González
Adriana
A
Cruzado
Montserrat
M
D000498:Allyl Compounds / Q000494:pharmacology*; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D005737:Garlic / Q000737:chemistry*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D017382:Reactive Oxygen Species / Q000378:metabolism; D013440:Sulfides / Q000494:pharmacology*
D000498:Allyl Compounds; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D013440:Sulfides; D000804:Angiotensin II; D050760:Cyclin-Dependent Kinase Inhibitor p27; C038491:allyl sulfide; D048049:Extracellular Signal-Regulated MAP Kinases; C077207:allyl methyl sulfide