|Nie, Lin - TUFTS/HNRCA|
|Peterson, David - ARS CEREAL CROPS|
Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: April 1, 2005
Publication Date: April 1, 2005
Citation: Nie, L., Wise, M., Peterson, D., Meydani, M. 2005. Mechanism by which avenanthramide-c, a polyphenol of oats, blocks cell cycle progression in vascular smooth muscle cells. Federation of American Societies for Experimental Biology Conference. 20:A1014. Technical Abstract: Avenanthramides (Avn) are unique polyphenols present in oats. We have reported that Avn-c, one of the major forms of Avn with the most antioxidant activity, inhibited the proliferation of vascular smooth muscle cells (SMC), an important process in the development of atherosclerosis and restenosis following angioplasty. Here we report that methyl ester of Avn-c (CH3-Avn-c) had a 10-fold higher potency than non-methylated form on the suppression of SMC proliferation. In the present study, we investigated the molecular mechanism by which Avn-c inhibits proliferation of SMC. Flow cytometry analysis revealed that treatment of A10 cells with 80 microM Avn-c arrested the cell cycle at G1 phase as indicated by an increase in the G1 cell population (from 49.7% to 66.9%) and a decrease in the number of cells in S phase (from 40% to 25.7%). This cell cycle arrest was associated with a decrease in the phosphorylation of retinoblastoma protein (pRb), whose hyperphosphorylation is a hallmark of the G1 to S transition in the cell cycle. The inhibition of pRb phosphorylation with Avn-c was accompanied by a decrease in cyclin D1 expression and an increase in p21cip1 expression, without significant changes in p27kip1 expression. Avn-c treatment also increased the expression level and stability of p53 protein, which could account for the increase of p21cip1 expression. Our results demonstrate that Avn-c inhibits SMC proliferation and arrests the cell cycle at G1 phase by up-regulating p53-p21cip1 pathway and inhibiting pRB phosphorylation. This inhibitory effect of Avn-c on SMC proliferation is another potential mechanism by which consumption of oats contributes to the prevention of cardiovascular disease.