Chemopreventive and antineoplastic activity of N-homocysteine thiolactonyl retinamide.

Abstract

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.

• Authors: K S McCully, M P Vezeridis
• Journal: Carcinogenesis (Carcinogenesis) Vol. 8 Issue 10 Pg. 1559-62 (Oct 1987) ISSN: 0143-3334 [Print] England
• PMID: 3652391 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antineoplastic Agents
• Homocysteine
• N-homocysteine thiolactonyl retinamide
• Urethane
• Tretinoin

Topics

• Animals
• Antineoplastic Agents (therapeutic use)
• Homocysteine (analogs & derivatives, pharmacology, therapeutic use)
• Lung Neoplasms (chemically induced, drug therapy)
• Mice
• Mice, Inbred A
• Mice, Inbred C57BL
• Neoplasm Transplantation
• Rhabdomyosarcoma (chemically induced, drug therapy)
• Solubility
• Tretinoin (analogs & derivatives, pharmacology, therapeutic use)
• Urethane