Inhibitory Effects of 9-(4-Thio-β- D -ribo-pentofuranosyl)guanine on Tumor Growth and Angiogenesis
2004
Background: To find a nucleoside with anti-angiogenic activity, we tried to screen an active compound from our nucleoside library. Materials and Methods: The compound inhibiting the growth of human umbilical vein endothelial cell (HUVEC) induced by the conditioned medium of lung carcinoma cell line PC-9 was screened. The antitumor activity of the compound was evaluated against murine sarcoma S-180 implanted onto chick embryo chorioallantoic membrane (CAM). Results: 9-(4-Thio-β-D-ribo-pentofuranosyl)guanine (4′-thioguanosine) was found to be a potent inhibitor of the growth of HUVEC. The growth of S-180 implanted onto CAM was also inhibited by 4′-thioguanosine whereas the in vitro growth of S-180 was not inhibited. The administration of 4′-thioguanosine in mice caused unexpected side effect which suggested neurotoxicity. Conclusions: Antitumor effect of 4′-thioguanosine on S-180 was suggested to be due to inhibition of tumor angiogenesis. Because of toxicity of 4′-thioguanosine in mice, further development of the derivatives which have lower toxicity is required.
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