Cytotoxic Effect of 8-Amino Adenosine 3', 5'-Cyclic Monophosphate on FM3A Mouse Mammary Tumor Cells

Abstract

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 μM with the ID₅₀ value of 4 μM. 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.