The possible mechanisms of the antiproliferative effect of fullerenol, polyhydroxylated C 60 , on vascular smooth muscle cells

• Published in: British journal of pharmacology Vol. 123; no. 6; pp. 1097 - 1102
• Main Authors: Lu, Liang‐Huei, Lee, Yuan‐Teh, Chen, Huei‐Wen, Chiang, Long Y., Huang, Huei‐Chen
• Format: Journal Article
• Language: English
• Published: 10.02.2009
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0701722

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 O 2 − 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. British Journal of Pharmacology (1998) 123 , 1097–1102; doi: 10.1038/sj.bjp.0701722