Antitumor activity of creatine analogs produced by alterations in pancreatic hormones and glucose metabolism.
When rats bearing the 13,762 mammary carcinoma were treated with intravenously administered creatine analogs, cyclocreatine, beta-guanidinopropionic acid or creatine phosphate on days 4 through 8 and 14 through 18 post tumor implantation, the tumor growth delay produced varied with whether the animals were drinking water or sugar water over the course of the study. The tumor growth delays increased when the animals drank sugar water from 9.3, 1.6 and 7.6 days for cyclocreatine, beta-guanidinopropionic acid and creatine phosphate, respectively, to 15.0, 6.3 and 12.6 days. Blood glucose was decreased over the course of the creatine analog treatment regimen and the skeletal muscle transport protein GLUT-4 increased 1.5 to 2-fold with the creatine analog treatments. Plasma insulin was profoundly decreased to 20-25% of normal by the creatine analog treatment while plasma glucagon levels were increased. Plasma somatostatin increased 3- to 4-fold during the administration of the creatine analogs. These results implicate alterations in pancreatic hormone balance in the antitumor activity of these creatine analogs.
Ara
G
G
Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Gravelin
L M
LM
Kaddurah-Daouk
R
R
Teicher
B A
BA
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003401:Creatine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003404:Creatinine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology; D007275:Injections, Intravenous; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism; D010187:Pancreatic Hormones / Q000378:metabolism*; D010725:Phosphocreatine / Q000008:administration & dosage / Q000494:pharmacology; D011422:Propionates / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D006146:Guanidines; D010187:Pancreatic Hormones; D011422:Propionates; D010725:Phosphocreatine; C012260:cyclocreatine; D003404:Creatinine; D005947:Glucose; D003401:Creatine; C005775:guanidinopropionic acid