Chemopreventive and antineoplastic activity of N-homocysteine thiolactonyl retinamide.
N-homocysteine thiolactonyl retinamide was synthesized from trans retinoic acid and the free base of homocysteine thiolactone. In doses of 90-1800 mg/kg given i.p. in mixed lipid vehicle over nine weeks, the compound decreased to 60% of controls the number of lung tumors which was induced in A/J mice by 20 mg of ethyl carbamate. The highest dose also decreased the mean volume of lung tumors to 50% of controls, resulting in a total tumor volume of 30% of controls. Retinoic acid itself at 450 mg/kg was toxic, and no chemopreventive activity was observed. The free base and the lipophilic perchlorate salt of homocysteine thiolactone both increased the number of lung tumors to 114-117% of controls, indicating a co-carcinogenic effect. In C57BL/6N mice with transplanted MUO4 rhabdomyosarcoma, N-homocysteine thiolactonyl retinamide in a dose of 1000 mg/kg given over 11-21 days decreased the weight of the tumors to 30-70% of controls. These results show that N-homocysteine thiolactonyl retinamide has chemopreventive activity against chemical carcinogenesis and antineoplastic activity against a transplanted neoplasm.
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000139:chemically induced / Q000188:drug therapy; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D012208:Rhabdomyosarcoma / Q000139:chemically induced / Q000188:drug therapy; D012995:Solubility; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014520:Urethane
D000970:Antineoplastic Agents; D006710:Homocysteine; C053232:N-homocysteine thiolactonyl retinamide; D014520:Urethane; D014212:Tretinoin