The alterations of enzymatic activities involved in
lipid degradation in
cancer cachexia have not been fully elucidated. One of the two subclones of colon 26
adenocarcinoma, clone 20, with a potent ability to induce
cachexia, or clone 5, without such an activity, was transplanted in to CDF-1 male mice. Murine livers were extirpated for analyses on the 14th day after
tumor inoculation. The
body weights and food intake of mice bearing clone 20 were all significantly lower than those of non-
tumor bearing mice and mice bearing the clone 5
tumor. The decline of
body weight was accompanied by a shrinkage of epididymal fat pads. Expression of
spermidine/
spermine N-1 acetyl
transferase (SSAT) assessed by real-time PCR was significantly increased in cachectic mice. Conversely,
acetyl-CoA carboxylase (ACC) measured by Western blotting and
malonyl-CoA levels determined by
malonyl-CoA:
acetyl-CoA cycling procedures were decreased in cachectic mice.
Indomethacin in
drinking water reversed the clone 20 induced decrease in body and fat weight and food intake, and simultaneously negated the clone 20 induced increase of SSAT expressions and decrease of ACC and
malonyl-CoA amounts. Because
malonyl-CoA inhibits the rate-limiting step in the beta-oxidation of
fatty acids, the decreased
malonyl-CoA and the background metabolic alterations may contribute to the accelerated lipolysis of
cancer cachexia.