Attenuation of proteolysis and muscle wasting by curcumin c3 complex in MAC16 colon tumour-bearing mice.
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 microg/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 microg/ml. Curcumin c3 at 2.5 microg/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.
Siddiqui
Rafat A
RA
Methodist Research Institute, Clarian Health Partners, Indianapolis, IN 46202, USA. rsiddiqu@clarian.org
Hassan
Samira
S
Harvey
Kevin A
KA
Rasool
Tamkeen
T
Das
Tapas
T
Mukerji
Pradip
P
DeMichele
Stephen
S
D000818:Animals; D002100:Cachexia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000150:complications*; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009133:Muscular Atrophy / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D032446:Myoblasts / Q000187:drug effects / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D015431:Weight Loss / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D009124:Muscle Proteins; D046988:Proteasome Endopeptidase Complex; D003474:Curcumin