Quercetin supplementation attenuates the progression of cancer cachexia in ApcMin/+ mice.
Although there are currently no approved treatments for cancer cachexia, there is an intensified interest in developing therapies because of the high mortality index associated with muscle wasting diseases. Successful treatment of the cachectic patient focuses on improving or maintaining body weight and musculoskeletal function. Nutraceutical compounds, including the natural phytochemical quercetin, are being examined as potential treatments because of their anti-inflammatory, antioxidant, and anticarcinogenic properties. The purpose of this study was to determine the effect of quercetin supplementation on the progression of cachexia in the adenomatous polyposis coli (Apc)(Min/+) mouse model of colorectal cancer. At 15 wk of age, C57BL/6 and male Apc(Min/+) mice were supplemented with 25 mg/kg of quercetin or vehicle solution mix of Tang juice and water (V) daily for 3 wk. Body weight, strength, neuromuscular performance, and fatigue were assessed before and after quercetin or V interventions. Indicators of metabolic dysfunction and inflammatory signaling were also assessed. During the treatment period, the relative decrease in body weight in the Apc(Min/+) mice gavaged with V (Apc(Min/+)V; -14% ± 2.3) was higher than in control mice gavaged with V (+0.6% ± 1.0), control mice gavaged with quercetin (-2% ± 1.0), and Apc(Min/+) mice gavaged with quercetin (Apc(Min/+)Q; -9% ± 1.3). At 18 wk of age, the loss of grip strength and muscle mass shown in Apc(Min/+)V mice was significantly attenuated (P < 0.05) in Apc(Min/+)Q mice. Furthermore, Apc(Min/+)V mice had an induction of plasma interleukin-6 and muscle signal transducer and activator of transcription 3 phosphorylation, which were significantly (P < 0.05) mitigated in Apc(Min/+)Q mice, despite having a similar tumor burden. Quercetin treatment did not improve treadmill run-time-to-fatigue, hyperglycemia, or hyperlipidemia in cachectic Apc(Min/+) mice. Overall, quercetin supplementation positively affected several aspects of cachexia progression in mice and warrants further exploration as a potential anticachectic therapeutic.
Division of Applied Physiology, Department of Exercise Science, and Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina, Columbia, SC.
Kandy T
KT
Velázquez
Division of Applied Physiology, Department of Exercise Science, and Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina, Columbia, SC.
Reilly T
RT
Enos
Division of Applied Physiology, Department of Exercise Science, and.
Aditi A
AA
Narsale
Division of Applied Physiology, Department of Exercise Science, and.
Melissa J
MJ
Puppa
Division of Applied Physiology, Department of Exercise Science, and.
J Mark
JM
Davis
Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina, Columbia, SC.
E Angela
EA
Murphy
Division of Applied Physiology, Department of Exercise Science, and carsonj@mailbox.sc.edu.
James A
JA
Carson
D000818:Animals; D001682:Biological Availability; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002100:Cachexia / Q000188:drug therapy*; D002851:Chromatography, High Pressure Liquid; D019587:Dietary Supplements; D004195:Disease Models, Animal; D018450:Disease Progression; D007328:Insulin / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009369:Neoplasms / Q000503:physiopathology*; D010766:Phosphorylation; D011794:Quercetin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D007328:Insulin; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D014280:Triglycerides; D011794:Quercetin