THE POSSIBLE MECHANISMS OF THE ANTIPROLIFERATIVE EFFECT OF FULLERENOL, POLYHYDROXYLATED C-60, ON VASCULAR SMOOTH-MUSCLE CELLS

1 The possible mechanisms of the antiproliferative effect of polyhydro xylated fullerene (fullerenol), a novel free radical trapper, were stu died in rat vascular smooth muscle cells (A7r5 cells) and compared wit h the effect of ascorbic acid. 2 Fullerenol-1 and ascorbic acid inhibi ted the proliferative responses in a number of cells, including rat ao rtic smooth muscle cells (A7r5 cells), human coronary artery smooth mu scle cells, and human CEM lymphocytes (CEM cells) in a concentration d ependent manner. 3 At the concentration range of 10(-6) to 10(-2) M, f ullerenol-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 O-2(-) induc ed by alloxan, a diabetogenic compound, was reduced by fullerenol-1 (1 0(-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 1 0(-3) M fullerenol-1, but not ascorbic acid (10(-4)-10(-2) M) and full erenol-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 Ou r results demonstrate that fullerenol-1 and ascorbic acid exhibit inhi bitory effects on transduction signals in addition to their antioxidat ive property. It is suggested that the antiproliferative effect of ful lerenol-1 on vascular smooth muscle cells may partly be mediated throu gh the inhibition of protein tyrosine kinase.