Aerobic exercise induces interleukin-6 and suppresses a marker of DNA damage, offering insight as to how it could reduce the risk of colon cancer
Aerobic exercise increases expression of interleukin-6 (IL-6) and suppresses the level of γ-H2AX, a marker for DNA damage, in a colon cancer cell line, providing a possible explanation as to how exercise reduces the risk of colon cancer. This was the conclusion of a study by a team from the School of Biomedical, Nutritional and Sport Sciences, Newcastle University, Newcastle upon Tyne, UK.
In 2020, globally, colon cancer was responsible for over 1.9 million cases and 0.9 million deaths. Moreover, there is evidence that physical activity reduces cancer risk and in 2018, the American physical activity guidelines advisory committee concluded that there is now strong evidence that physical activity lowers the risk of seven types of cancer (namely colon, breast, kidney, endometrium, bladder, and stomach cancer, and oesophageal adenocarcinoma) although this evidence is derived from epidemiological studies.
Aerobic exercise is a form of physical activity and an accumulating body of evidence suggests that the incubation of cancer cells with post-exercise serum can have powerful effects on key hallmarks of cancer cell behaviour in vitro. I
n fact, a 2020 systematic review concluded that the transient serological responses to acute exercises reduce cancer cell growth, although many questions remain regarding the underlying mechanistic pathways and potential effect modifiers.
Nevertheless, while the evidence suggests a beneficial effect on cancer risk, in order to achieve a better understanding of how aerobic exercise affects the biological processes involved in cancer, requires comparison with a control group.
For the present study, the UK team recruited men with lifestyle risk factors for colon cancer e.g., older than 50 years of age, with a body mass index (BMI) > than 25 or a waist circumference > 94 cm and who did not engage in > 30 minutes of moderate physical activity at least 3 days/week over the previous 3 months.
The same participants served as their own control and undertook aerobic activity (6 x 5 minutes of cycling) and a control intervention (60 minutes of a quiet rested sitting), which was separated by a period of 2 to 7 days.
The team used LoVo cells, which served as a model of colon cancer and the primary outcome of the study was the mean difference in LoVo cell proliferation between exercise and control conditions. A total of 7 cytokines were quantified including interleukins (IL-) 6, 8 and 10 as well as markers of DNA damage such as γ-H2AX, were assessed.
Aerobic exercise and LoVo cell response
A total of 16 men with a mean age of 60 years and mean BMI of 29.9 were included in the study.
After stimulation of the LoVo cells with post-exercise serum, there was a decrease in cell proliferation compared to pre-exercise serum (-4.2%, 95% CI -6.8 to -1.5%, p = 0.006). In contrast, during the control period, there was a post-control increase in cell proliferation compared to pre-control serum (5.4%, 95% CI 2.2 to 8.6%, p = 0.003).
After adjustment for pre-values, the authors calculated that exercise-conditioned serum reduced cell proliferation compared to control by 5.7% (95% CI -8.8 to -2.6%, p = 0.002).
Turning to changes in biological markers, the researchers found that exercise reduced levels of γ-H2AX by 24% (p = 0.029) which reflected a decrease in DNA damage. In addition, the acute bout of aerobic exercise only significantly increased expression of one marker, IL-6, by 24.6% (p = 0.002).
The authors concluded the increased IL-6 expression may help explain the observed benefits of aerobic exercise in epidemiological studies and could account for why exercise helps to reduce colon cancer risk.
Orange ST et al. Acute aerobic exercise‐conditioned serum reduces colon cancer cell proliferation in vitro through interleukin‐6‐induced regulation of DNA damage Int J Cancer 2022