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

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 vs nonexercise 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 × 5 minutes intervals at 60% heart rate reserve) and a nonexercise control condition. Stimulating LoVo cells with serum obtained immediately after exercise reduced cancer cell proliferation compared to control (-5.7%; P = .002). This was accompanied by a decrease in LoVo cell γ-H2AX expression (-24.6%; P = .029), indicating a reduction in DNA damage. Acute exercise also increased serum IL-6 (24.6%, P = .002). Furthermore, stimulating LoVo cells with recombinant IL-6 reduced γ-H2AX expression (β = -22.7%; P < .001) and cell proliferation (β = -5.3%; P < .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.

SUBMITTER: Orange ST

PROVIDER: S-EPMC9314683 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundExercise is widely recognised for its health enhancing benefits. Despite this, an overproduction of reactive oxygen and nitrogen species (RONS), outstripping antioxidant defence mechanisms, can lead to a state of (chronic) oxidative stress. DNA is a vulnerable target of RONS attack and, if left unrepaired, DNA damage may cause genetic instability.ObjectiveThis meta-analysis aimed to systematically investigate and assess the overall effect of studies reporting DNA damage following acute aerobic exercise.MethodsWeb of Science, PubMed, MEDLINE, EMBASE, and Scopus were searched until April 2019. Outcomes included (1) multiple time-points (TPs) of measuring DNA damage post-exercise, (2) two different quantification methods (comet assay and 8-oxo-2'-deoxyguanosine; 8-OHdG), and (3) protocols of high intensity (??75% of maximum rate of oxygen consumption; VO2-max) and long distance (??42 km).ResultsLiterature search identified 4316 non-duplicate records of which 35 studies were included in the meta-analysis. The evidence was strong, showcasing an increase in DNA damage immediately following acute aerobic exercise with a large-effect size at TP 0 (0 h) (SMD?=?0.875; 95% CI 0.5, 1.25; p?<?0.05). When comparing between comet assay and 8-OHdG at TP 0, a significant difference was observed only when using the comet assay. Finally, when isolating protocols of long-distance and high-intensity exercise, increased DNA damage was only observed in the latter. (SMD?=?0.48; 95% CI - 0.16, 1.03; p?=?0.15 and SMD?=?1.18; 95% CI 0.71, 1.65; p?<?0.05 respectively).ConclusionsA substantial increase in DNA damage occurs immediately following acute aerobic exercise. This increase remains significant between 2 h and 1 day, but not within 5-28 days post-exercise. Such an increase was not observed in protocols of a long-distance. The relationship between exercise and DNA damage may be explained through the hormesis theory, which is somewhat one-dimensional, and thus limited. The hormesis theory describes how exercise modulates any advantageous or harmful effects mediated through RONS, by increasing DNA oxidation between the two end-points of the curve: physical inactivity and overtraining. We propose a more intricate approach to explain this relationship: a multi-dimensional model, to develop a better understanding of the complexity of the relationship between DNA integrity and exercise.

Project description:Prevalence of iron deficiency is commonly reported among athletic population groups. It impairs physical performance due to insufficient oxygen delivery to target organs and low energy production. This is due to the high demand of exercise on oxygen delivery for systemic metabolism by the erythrocytes in the blood. Hepcidin, the key regulator of iron homeostasis, decreases to facilitate iron efflux into the circulation during enhanced erythropoiesis. However, acute anaemia of exercise is caused by increased hepcidin expression that is induced by stress and inflammatory signal. The study aimed to systematically review changes in serum hepcidin levels during resistance and aerobic exercise programmes. A systemic literature search from 2010 to April 2020 across seven databases comprised of Cochrane library, PubMed, Web of Science, Scopus, Embase, MEDLINE, and OpenGrey. The primary outcome was increased or decreased serum hepcidin from baseline after the exercise activity. Risks of bias were evaluated by using the National Institutes of Health (NIH) for quality assessment of before and after different exercise programmes. Overall, twenty-three studies met the inclusion criteria. Out of the 23 studies, 16 studies reported significantly exercise-induced serum hepcidin elevation. Of the 17 studies that evaluated serum interleukin (IL)-6 levels, 14 studies showed significant exercise-induced serum IL-6 elevation. Changes in exercise-induced serum hepcidin and IL-6 levels were similar in both resistance and endurance exercise. Significant correlations were observed between post-exercise hepcidin and baseline ferritin levels (r = 0.69, p < 0.05) and between post-exercise hepcidin and post-exercise IL-6 (r = 0.625, p < 0.05). Resistance and endurance training showed significant increase in serum hepcidin and IL-6 levels in response to exercise. Baseline ferritin and post-exercise IL-6 elevation are key determining factors in the augmentation of hepcidin response to exercise.

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

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