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.
Miura
Shinji
S
Biochemicals Division, Yamasa Corporation, 2-10-1 Araoi-cho, Choshi, Chiba 288-0056, Japan. miura@yamasa.com
Yamada
Kohei
K
Kano
Fumitaka
F
Yoshimura
Yuichi
Y
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply; D002823:Chorion / Q000187:drug effects; D003510:Cyclohexanes; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D012717:Sesquiterpenes; D014183:Transplantation, Heterologous
C493500:9-(4-thio-beta-D-ribo-pentofuranosyl)guanine; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D003510:Cyclohexanes; D005231:Fatty Acids, Unsaturated; D012717:Sesquiterpenes; D006147:Guanine; C026211:fumagillin