Inhibitory effects of 9-(4-thio-beta-D-ribo-pentofuranosyl)guanine on tumor growth and angiogenesis.

BACKGROUND

To find a nucleoside with anti-angiogenic activity, we tried to screen an active compound from our nucleoside library.

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.