The possible mechanisms of the antiproliferative effect of fullerenol, polyhydroxylated C60, on vascular smooth muscle cells.
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.
Lu
L H
LH
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei.
Lee
Y T
YT
Chen
H W
HW
Chiang
L Y
LY
Huang
H C
HC
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D002244:Carbon / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004789:Enzyme Activation; D037741:Fullerenes; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D013481:Superoxides / Q000378:metabolism
D037741:Fullerenes; D013481:Superoxides; C108127:fullerenol; D002244:Carbon; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D001205:Ascorbic Acid