Orange, Sam, Jordan, Alastair ORCID: https://orcid.org/0000-0002-7669-4753, Odell, Adam ORCID: https://orcid.org/0000-0002-6855-7214, Kavanagh, Owen ORCID: https://orcid.org/0000-0002-2599-8511, Hicks, Kirsty M., Eaglen, Tristan, Todryk, Stephen and Saxton, John M. (2022) Acute aerobic exercise-conditioned serum reduces colon cancer cell proliferation through IL-6-induced regulation of DNA damage in vitro. International Journal of Cancer, 151 (2). pp. 265-274.

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Abstract

Epidemiological evidence shows that regular physical activity is associated with reduced risk of primary and recurrent colon cancer. However, the underlying mechanisms of action are poorly understood. We evaluated the effects of stimulating a human colon cancer cell line (LoVo) with human serum collected before and after an acute exercise bout versus non-exercise control serum on cancer cell proliferation. We also measured exercise-induced changes in
serum cytokines and intracellular protein expression to explore potential biological mechanisms. Blood samples were collected from 16 men with lifestyle risk factors for colon
cancer (age ≥50 years; body mass index ≥25 kg/m2; physically inactive) before and immediately after an acute bout of moderate-intensity aerobic interval exercise (6 x 5 min
intervals at 60% heart rate reserve) and a non-exercise control condition. Stimulating LoVo cells with serum obtained immediately after exercise reduced cancer cell proliferation compared with control (-5.7%; p=0.002). This was accompanied by a decrease in LoVo cell γ-H2AX expression (-24.6%; p=0.029), indicating a reduction in DNA damage. Acute exercise also increased serum IL-6 (24.6%, p=0.002). Furthermore, stimulating LoVo cells with recombinant IL-6 reduced γ-H2AX expression (β=-22.7%; p<0.001) and cell proliferation (β=-5.3%; p<0.001) in a linear dose-dependent manner, mimicking the effect of exercise. These findings suggest that the systemic responses to acute aerobic exercise inhibit colon cancer cell proliferation in vitro, and this may be driven by IL-6-induced regulation of DNA damage and repair. This mechanism of action may partly underlie epidemiological associations linking regular physical activity with reduced colon cancer risk.

Item Type:	Article
Status:	Published
DOI:	10.1002/ijc.33982
Subjects:	Q Science > QP Physiology R Medicine > R Medicine (General) R Medicine > RM Therapeutics. Pharmacology
School/Department:	School of Science, Technology and Health
URI:	https://ray.yorksj.ac.uk/id/eprint/5945

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