11-acetyl-8-carbamoyloxymethyl-4-formyl-6-methoxy-14-oxa-1-11-diazatetracyclo(7.4.1.0.0)tetradeca-2-4-6-trien-9-yl-acetate and Cachexia

The effects of FK317 (11-acetyl-8-carbamoyloxymethyl-4-formyl-6- methoxy-14-oxa-1,11-diazatetracyclo[7.4.1.0(2, 7). 0(10, 2] tetradeca-2,4,6-trien-9-yl acetate), a novel anti-cancer agent, on murine adenocarcinoma colon26- and human lung carcinoma LX-1-induced cachexia were investigated in mice. Mice bearing colon26 or LX-1 s.c. lost weight and became cachectic, associated with tumor growth. FK317 and mitomycin C (MMC) inhibited the growth of both tumors. FK317 ameliorated the weight loss induced by the presence of colon26 or LX-1, while MMC enhanced it. An attenuation of the reduction in the weights of epididymal fat, gastrocnemius muscle and carcass was observed in FK317-treated tumor-bearing mice in both cachexia models, but not in MMC-treated mice. The decreases in the circulating levels of triglyceride, glucose and non-esterified fatty acid, which were induced by the presence of colon26, was partially inhibited by treatment with FK317. Overall, this study revealed that FK317 is a potent anti-cancer drug with anti-cachectic activity, suggesting that FK317 has potential utility for the treatment of cancer.

Topics: Adenocarcinoma; Adipose Tissue; Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Blood Glucose; Body Weight; Cachexia; Carcinoma; Colonic Neoplasms; Drug Screening Assays, Antitumor; Epididymis; Fatty Acids, Nonesterified; Female; Humans; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Mitomycin; Muscle, Skeletal; Organ Size; Oxazines; Triglycerides