Objective Several epidemiological studies have shown that regular exercise can prevent the onset of colon cancer, although the underlying mechanism is unclear. Myokines are secreted skeletal muscle proteins responsible for some exercise-induced health benefits including metabolic improvement and anti-inflammatory effects in organs. The purpose of this study was to identify new myokines that contribute to the prevention of colon tumorigenesis.
Methods To identify novel secreted muscle-derived proteins, DNA microarrays were used to compare the transcriptome of muscle tissue in sedentary and exercised young and old mice. The level of circulating secreted protein acidic and rich in cysteine (SPARC) was measured in mice and humans that performed a single bout of exercise. The effect of SPARC on colon tumorigenesis was examined using SPARC-null mice. The secretion and function of SPARC was examined in culture experiments.
Results A single bout of exercise increased the expression and secretion of SPARC in skeletal muscle in both mice and humans. In addition, in an azoxymethane-induced colon cancer mouse model, regular low-intensity exercise significantly reduced the formation of aberrant crypt foci in wild-type mice but not in SPARC-null mice. Furthermore, regular exercise enhanced apoptosis in colon mucosal cells and increased the cleaved forms of caspase-3 and caspase-8 in wild-type mice but not in SPARC-null mice. Culture experiments showed that SPARC secretion from myocytes was induced by cyclic stretch and inhibited proliferation with apoptotic effect of colon cancer cells.
Conclusions These findings suggest that exercise stimulates SPARC secretion from muscle tissues and that SPARC inhibits colon tumorigenesis by increasing apoptosis.
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Funding This work was supported by Grants-in-Aid from the Japan Society for the Promotion of Science (23700776WA, 08101559YN and 21390184TY) from the Ministry of Education, Culture, Sports, Science and Technology of Japan and research grants from the Adaptable and Seamless Technology Transfer Program through Target Driven R&D from the Japan Science and Technology Agency, Kyoto Prefectural University Corporation, Nakatomi Foundation and Uehara Memorial Foundation.
Correction notice This article has been corrected since it was published Online First. The following sentence has been amended to read: SPARC demonstrated accelerated cell proliferation compared with medium obtained from normal muscle cells (figure 5C).
Competing interests None.
Patient consent Obtained.
Ethics approval The experimental protocol was approved by the Review Board on Human Experiments, Kyoto Prefectural University and complied with the Helsinki Declaration.
Provenance and peer review Not commissioned; externally peer reviewed.
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