British Journal of Nutrition

Full Papers

Molecular Nutrition

Attenuation of proteolysis and muscle wasting by curcumin c3 complex in MAC16 colon tumour-bearing mice

Rafat A. Siddiquia1 c1, Samira Hassana1, Kevin A. Harveya1, Tamkeen Rasoola1, Tapas Dasa2, Pradip Mukerjia2 and Stephen DeMichelea2

a1 Methodist Research Institute, Clarian Health Partners, 1800 N. Capitol Avenue, Indianapolis, IN 46202, USA

a2 Research and Development, Abbott Nutrition, Abbott Laboratories, Columbus, OH 43215, USA

Abstract

Muscle wasting or cachexia is caused by accelerated muscle protein breakdown via the ubiquitin–proteasome complex. We investigated the effect of curcumin c3 complex (curcumin c3) on attenuation of muscle proteolysis using in vitro and in vivo models. Our in vitro data indicate that curcumin c3 as low as 0·50 μg/ml was very effective in significantly inhibiting (30 %; P < 0·05) tyrosine release from human skeletal muscle cells, which reached a maximum level of inhibition of 60 % (P < 0·05) at 2·5 μg/ml. Curcumin c3 at 2·5 μg/ml also inhibited chymotrypsin-like 20S proteasome activity in these cells by 25 % (P < 0·05). For in vivo studies, we induced progressive muscle wasting in mice by implanting the MAC16 colon tumour. The in vivo data indicate that low doses of curcumin c3 (100 mg/kg body weight) was able to prevent weight loss in mice bearing MAC16 tumours whereas higher doses of curcumin c3 (250 mg/kg body weight) resulted in approximately 25 % (P < 0·05) weight gain as compared with the placebo-treated animals. Additionally, the effect of curcumin c3 on preventing and/or reversing cachexia was also evident by gains in the weight of the gastrocnemius muscle (30–58 %; P < 0·05) and with the increased size of the muscle fibres (30–65 %; P < 0·05). Furthermore, curcumin inhibited proteasome complex activity and variably reduced expression of muscle-specific ubiquitin ligases: atrogin-1/muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MURF-1). In conclusion, oral curcumin c3 results in the prevention and reversal of weight loss. The data imply that curcumin c3 may be an effective adjuvant therapy against cachexia.

(Received October 17 2008)

(Revised March 18 2009)

(Accepted March 19 2009)

(Online publication April 27 2009)

Correspondence:

c1 Corresponding author: Dr Rafat A. Siddiqui, fax +1 317 962 6941, email rsiddiqu@clarian.org

Footnotes

Abbreviations: LPS, lipopolysacchride; MAFbx, muscle atrophy F-box; MURF-1, muscle RING finger 1; SkBM, Skeletal Muscle Cell Basal Medium; Tris, 2-amino-2-hydroxymethyl-propane-1,3-diol