The possible mechanisms of the antiproliferative effect of fullerenol, polyhydroxylated C60, on vascular smooth muscle cells
Journal
British Journal of Pharmacology
Journal Volume
123
Journal Issue
6
Pages
1097-1102
Date Issued
1998
Author(s)
Abstract
1. 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. 2. 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. 3. 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. 4. The production of O2- induced by alloxan, a diabetogenic compound, was reduced by fullerenol-1 (10-4 M) in the presence of A7r5 cells. 5. 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). 6. 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. 7. 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.
Subjects
Antioxidant; Antiproliferative effect; Ascorbic acid; Fullerenol; Protein kinase C; Protein tyrosine kinase; Smooth muscle cells (vascular)
SDGs
Other Subjects
alloxan; antimitotic agent; ascorbic acid; free radical; fullerene derivative; fullerenol; hydroxyl radical; phorbol ester; protein kinase c; protein tyrosine kinase; unclassified drug; animal cell; aorta; article; concentration response; controlled study; coronary artery; enzyme activity; human; human cell; lymphocyte; nonhuman; priority journal; rat; signal transduction; smooth muscle fiber; vascular smooth muscle; Animals; Ascorbic Acid; Carbon; Cell Division; Cell Line; Enzyme Activation; Fullerenes; Humans; Muscle, Smooth, Vascular; Protein Kinase C; Protein-Tyrosine Kinases; Rats; Superoxides
Type
journal article