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, 8-chloroadenosine 3',5'-cyclic monophosphate (8-Cl-cyclic AMP) when given by alzet 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.
Ramage
A D
AD
ICRF Medical Oncology Unit, Western General Hospital, Edinburgh, U.K.
Langdon
S P
SP
Ritchie
A A
AA
Burns
D J
DJ
Miller
W R
WR
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007165:Immunosuppression Therapy; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D015124:8-Bromo Cyclic Adenosine Monophosphate; C044258:8-chloro-cyclic adenosine monophosphate; D017868:Cyclic AMP-Dependent Protein Kinases