Antineoplastic activity of N-maleamide homocysteine thiolactone amide encapsulated within liposomes.
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 less than 0.005) and in C57B1/6N males with MUO4 rhabdomyosarcoma (11% of control value, P less than 0.0000001). Tumor incidence was reduced from 84 to 63% (P less than 0.05) and from 100 to 32% (P less than 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 less than 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.
D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D005260:Female; D006710:Homocysteine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008081:Liposomes / Q000008:administration & dosage*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D012208:Rhabdomyosarcoma / Q000188:drug therapy*
D008081:Liposomes; D006710:Homocysteine; C046361:N-maleamide homocysteine thiolactome amide