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Acute aerobic exercise-conditioned serum reduces colon cancer cell proliferation in vitro through interleukin-6-induced regulation of DNA damage

Lookup NU author(s): Dr Sam OrangeORCiD, Dr Stephen Todryk



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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 colorectal 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.

Publication metadata

Author(s): Orange ST, Jordan AR, Odell A, Kavanagh O, Hicks KM, Eaglen T, Todryk S, Saxton JM

Publication type: Article

Publication status: Published

Journal: International Journal of Cancer

Year: 2022

Volume: 151

Issue: 2

Pages: 265-274

Print publication date: 15/07/2022

Online publication date: 25/02/2022

Acceptance date: 11/02/2022

Date deposited: 14/02/2022

ISSN (print): 0020-7136

ISSN (electronic): 1097-0215

Publisher: John Wiley & Sons, Inc.


DOI: 10.1002/ijc.33982


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