Antineoplastic Activity of N-maleamide Homocysteine Thiolactone Amide Encapsulated within Liposomes

Abstract

The antineoplastic activity of N-maleamide homocysteine thiolactone amide (MHTA) encapsulated within liposomes was studied in mice with transplanted tumors. Tumor weight was decreased by 4-5 biweekly intraperitoneal injections of MHTA in liposomes in DBA/2N females with MTG mammary adenocarcinoma (35% of control value, P < 0.005) and in C57B1/6N males with MU04 rhabdomyosarcoma (11% of control value, P < 0.0000001). Tumor incidence was reduced from 84 to 63% (P < 0.05) and from 100 to 32% (P < 0.001) in the two systems, respectively. When the compound was administered in dimethyl sulfoxide to A/HeJ females with A10 mammary adenocarcinoma by daily intraperitoneal injection, tumor weight was reduced to 70% of control value (P < 0.05), and there was no decrease in tumor incidence (100%). No toxicity was observed at the therapeutic dose utilized, 10 mg/kg/ day. N-Maleamide homocysteine thiolactone amide is a derivative of the normal biochemical constituents, maleic acid and homocysteine thiolactone. The results show that the N-substituted maleamide derivative of homocysteine thiolactone decreases the growth of murine tumors of two different histological types, when administered encapsulated within liposomes.