Inhibitory effects of 9-(4-thio-beta-D-ribo-pentofuranosyl)guanine on tumor growth and angiogenesis |
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Authors: | Miura Shinji Yamada Kohei Kano Fumitaka Yoshimura Yuichi |
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Institution: | Biochemicals Division, Yamasa Corporation, 2-10-1 Araoi-cho, Choshi, Chiba 288-0056, Japan. miura@yamasa.com |
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Abstract: | 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-beta-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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