Abstract
PURPOSE: Regular physical activity protects against the development of cancer. This is in particular true for breast and colon cancer, where regular physical activity can reduce the risk of developing these with 25-30%. The mechanisms whereby physical activity protects against cancer are practically unknown. During exercise, humoral factors, known as myokines, are released from the working muscles to signal to other organs in an endocrine fashion. We hypothesized that these myokines may play a role in mediating the inhibitory effect of exercise on mammary cancer cell proliferation. METHODS AND RESULTS: Serum and muscles were collected from mice following one hour of swimming exercise. Incubation with serum obtained after exercise inhibited the growth of the MCF-7 mammary cancer cell line by 52% and increased caspase activity with 54%. PCR array analysis (CAPM-0838E, SABiosciences) revealed that 8 genes were up- regulated in the muscles after one hour of swimming, and of these Oncostatin M (OSM) proved to inhibit MCF-7 cell growth by 42%, increase caspase activity by 53% and induce apoptosis as determined by annexin-streptavidin staining. To verify that OSM was a myokine, we measured serum OSM concentrations and OSM expression in several tissues following a bout of swimming exercise. OSM was significantly up-regulated in serum and in the 3 muscles: tibialis cranialis, gastronemius and soleus. In contrast, OSM expression remained unchanged in subcutaneous and visceral adipose tissue, liver and spleen (mononuclear cells) after the swimming exercise bout. CONCLUSION: post exercise serum inhibits mammary cancer cell proliferation and induces apoptosis of these cells. We suggest that one or more myokines secreted from working muscles, may be mediating this effect and that OSM is a possible candidate.
Published Version
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