RT Journal Article
SR Electronic
T1 Diosgenin Modulates Vascular Smooth Muscle Cell Function by Regulating Cell Viability, Migration, and Calcium Homeostasis
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 925
OP 939
DO 10.1124/jpet.110.172684
VO 336
IS 3
A1 Mitra Esfandiarei
A1 Julia T. N. Lam
A1 Sahar Abdoli Yazdi
A1 Amina Kariminia
A1 Jorge Navarro Dorado
A1 Boris Kuzeljevic
A1 Harley T. Syyong
A1 Kaiji Hu
A1 Cornelis van Breemen
YR 2011
UL http://jpet.aspetjournals.org/content/336/3/925.abstract
AB In this study, we compared the potencies of diosgenin, a plant-derived sapogenin structurally similar to estrogen and progesterone, on vascular smooth muscle functions ranging from contraction and migration to apoptosis. The effects of diosgenin on vascular smooth muscle cell viability and migration were measured using a primary mouse aortic smooth muscle cell culture. The effects of diosgenin on smooth muscle cell contraction and calcium signaling were investigated in the isolated mouse aorta using wire myography and confocal microscopy, respectively. Here, we report that in cultured cells diosgenin (≥25 μM) induces apoptosis as measured by the number of annexin V-positive cells and caspase-3 cleavage, while decreasing cell viability as indicated by protein kinase B/Akt phosphorylation. In addition, diosgenin blocks smooth muscle cell migration in a transwell Boyden chamber in response to serum treatment and response to injury in a cell culture system. Diosgenin (≥25 μM) also significantly blocks receptor-mediated calcium signals and smooth muscle contraction in the isolated aorta. There is no difference in the inhibitory effects of diosgenin on vascular smooth muscle contraction between the endothelium-intact and endothelium-denuded aortic segments, indicating that they are caused by altered smooth muscle activity. Our findings suggest that over the concentration range of 10 to 15 μM diosgenin may provide overall beneficial effects on diseased vascular smooth muscle cells by blocking migration and contraction without any significant cytopathic effects, implying a potential therapeutic value for diosgenin in vascular disorders.