Inhibition of neoplastic growth by N-homocysteine thiolactonyl retinamido cobalamin.
Because of the importance of homocysteine thiolactone metabolism in the growth of normal tissues, and because of abnormal metabolism of homocysteine thiolactone in malignant cells, N-substituted derivatives of homocysteine thiolactone were synthesized and assayed for antineoplastic and anticarcinogenic activities. A single dose of 2.5 mg/kg of the synthetic derivative, N-homocysteine thiolactonyl retinamido cobalamin, injected directly into subcutaneous human pancreatic adenocarcinoma neoplasms in athymic mice, caused 50% inhibition of growth without evidence of toxicity. The findings suggest a novel approach to counteracting the growth of malignant neoplasms and support the hypothesis of a deficiency of an N-homocysteine thiolactonyl derivative in malignant cells.
McCully
K S
KS
Veterans Administration Medical Center, Providence RI 02908.
Tzanakakis
G N
GN
Vezeridis
M P
MP
D000230:Adenocarcinoma; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology*; D010190:Pancreatic Neoplasms; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000494:pharmacology
D000970:Antineoplastic Agents; C062732:N-homocysteine thiolactonyl retinamido cobalamin; D006710:Homocysteine; D014805:Vitamin B 12