NMR-based metabolomics reveals distinct pathways mediated by curcumin in cachexia mice bearing CT26 tumor

Abstract

Background: cachexia is common in cancer patients, with profound metabolic abnormalities in response to malignant growth of cancer and progressive catabolism of host. Previous studies showed pharmacodynamics efficacy of curcumin in the prevention and treatment of cancer cachexia. However, the metabolic regulation effect is still unknown. Methods: we employed a proton NMR-metabonomics method to investigate the metabolic features of cancer cachexia and the contribution of curcumin to serum metabolites in a mouse model bearing CT26 tumor. Results: curcumin treatment (200 mg per kg per day) resulted in 13.9% less body weight loss and conserved mass of epididymal fat, muscle gastrocnemius and muscle tibialis anterior 91.4%, 11.5%, and 13.7% respectively in cancer cachexia mice. Proton NMR-based metabolomics revealed the altered metabolic profile and found 25 sensitive metabolites associated with cancer cachexia. Moreover, curcumin treatment resulted in metabolic reprogramming including decrease of phenylalanine, alanine, carnosine, carnitine, taurine, S-sulfocysteine, citrate, malate, glucose, and increase of citrulline, valine, isoleucine, methionine, glycine, acetoacetate and lactate. The pathway analysis showed that the main metabolic regulation of curcumin involved the metabolism of valine, leucine and phenylanaline, and synthesis and degradation of ketone bodies. Conclusions: these altered metabolic pathways imply a highly specific metabolism regulation of curcumin and raise the possibility for its therapeutic effect on alleviating cachexia hypermetabolism.