GROWTH-INHIBITION BY 8-CHLORO CYCLIC-AMP OF HUMAN HT29 COLORECTAL AND ZR-75-1 BREAST-CARCINOMA XENOGRAFTS IS ASSOCIATED WITH SELECTIVE MODULATION OF PROTEIN-KINASE-A ISOENZYMES

Significant dose-related inhibition of growth of HT29 human colorectal cancer xenografts and ZR-75-1 breast cancer xenografts in immune-suppressed mice was induced by the cyclic AMP analogue, and chloroadenosine 3',5'-cyclic monophosphate (8-Cl-cyclic AMP) when given by abet mini-pumps over a 7-day period at doses of either 50 or 100 mg/kg/day. Levels and types of cyclic AMP binding proteins were measured by Ligand binding and photoaffinity labelling, respectively, in tumours harvested at the end of the treatment period. Compared with levels in tumours from control animals, values of tumour cyclic AMP binding proteins from treated animals were significantly reduced. These effects were associated with an apparent modulation of the types of cyclic AMP binding proteins, 8-Cl-cyclic AMP-treated xenografts displaying a reduced ratio of RI/RII isoforms compared with untreated control tumours.