Cytotoxic effect of 8-amino adenosine 3',5'-cyclic monophosphate on FM3A mouse mammary tumor cells.
Derivatives of adenosine 3',5'-cyclic monophosphate (cAMP) with modifications at the 8-position were synthesized and examined for their cytotoxic effects on FM3A mouse mammary tumor cells and ZR-75 human mammary tumor cells. On in vitro tests of these derivatives, 8-amino (8-NH2) cAMP was the most effective against both cell lines. This compound showed the dose-dependent inhibition of FM3A cell growth in the concentration of over 2.5 microM with the ID50 value of 4 microM. Furthermore, antitumor activity of 8-NH2 cAMP was also tested against FM3A cells in vivo. T/C% values of 8-NH2 cAMP were respectively 162% and 138% in response to doses of 30 and 10 mg/kg by intraperitoneal injections of 8-NH2 cAMP for 5 d. 8-NH2 cAMP was converted to 8-NH2 adenosine via 8-NH2 adenosine 5'-monophosphate by some enzymes in the fetal bovine serum and the cytotoxic effect of 8-NH2 cAMP on FM3A cells was actually stemmed from 8-NH2 adenosine.
Saito
M
M
Noda Institute for Scientific Research, Chiba-ken, Japan.
Nasu
A
A
Kataoka
S
S
Ohshita
K
K
Yamaji
N
N
D000818:Animals; D000970:Antineoplastic Agents; D002851:Chromatography, High Pressure Liquid; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004176:Dipyridamole / Q000494:pharmacology; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004176:Dipyridamole; D000242:Cyclic AMP