Abstract
The possible mechanisms of the antiproliferative effect of polyhydroxylated fullerene (fullerenol), a novel free radical trapper, were studied in rat vascular smooth muscle cells (A7r5 cells) and compared with the effect of ascorbic acid.
Fullerenol-1 and ascorbic acid inhibited the proliferative responses in a number of cells, including rat aortic smooth muscle cells (A7r5 cells), human coronary artery smooth muscle cells, and human CEM lymphocytes (CEM cells) in a concentration dependent manner.
At the concentration range of 10−6 to 10−2 M, fullerenol-1 and ascorbic acid concentration-dependently inhibited the proliferative responses stimulated by serum in A7r5 cells. Fullerenol-1 was more potent than ascorbic acid.
The production of O2− induced by alloxan, a diabetogenic compound, was reduced by fullerenol-1 (10−4 M) in the presence of A7r5 cells.
The cytosolic protein kinase C activity of A7r5 cells stimulated by phorbol ester was reduced by 10−3 M fullerenol-1, but not ascorbic acid (10−4–10−2 M) and fullerenol-1 at lower concentrations (10−6–10−4 M).
In contrast, the membraneous protein tyrosine kinase activity of A7r5 cells stimulated by foetal calf serum was significantly reduced by fullerenol-1 (10−6–10−3 M) and ascorbic acid (10−4–10−2 M). Again, the inhibitory activity of fullerenol-1 was greater than that of ascorbic acid.
Our results demonstrate that fullerenol-1 and ascorbic acid exhibit inhibitory effects on transduction signals in addition to their antioxidative property. It is suggested that the antiproliferative effect of fullerenol-1 on vascular smooth muscle cells may partly be mediated through the inhibition of protein tyrosine kinase.
Keywords: Antiproliferative effect, fullerenol, ascorbic acid, antioxidant, protein tyrosine kinase, protein kinase C, smooth muscle cells (vascular)
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