Inhibitory Effects of 9-(4-Thio-β-D-ribo-pentofuranosyl) guanine on Tumor Growth and Angiogenesis (Pharmacology)

概要

論文の詳細を見る
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.
公益社団法人日本薬学会の論文
2004-04-01