Acute exercise triggers circulating changes that improve DNA damage repair and remodel gene expression in colon cancer cells, as revealed by a recent UK-US collaboration.
Although frequent physical activity is known to slow the progression of colon cancer, the mechanisms behind this benefit remained unclear.
Now, research led by teams at Newcastle and Teesside Universities has investigated how acute exercise alters the systemic environment, as well as characterising the proteomic response to intense exercise and determining whether exercise-conditioned human serum affects DNA damage repair and gene expression in colon cancer cells.
The study, published in the International Journal of Cancer, included 30 apparently healthy adults aged 50–78 years, all classified as overweight or obese (body mass index 25–39.9 kg/m²). Participants completed a maximal incremental cycling test, with blood samples being collected immediately before and within one minute of the exercise session.
Serum from these paired samples was then used to treat LoVo colon cancer cells, which harbour APC and KRAS mutations and display characteristics of early-stage tumour biology. Cells were exposed to 2 Gy of ionising radiation to induce double-strand DNA breaks, and DNA damage kinetics – assessed using γ-H2AX foci – were monitored over 24 hours.
The researchers also performed RNA sequencing of cells treated with pre- and post-exercise serum and profiled changes in 249 inflammatory and vascular proteins in serum by multiplex proteomic analysis.
Significantly elevated DNA repair after acute exercise
Post-exercise serum was found to significantly accelerate DNA repair in colon cancer cells. γ-H2AX foci were reduced by 16.8% at six hours after irradiation (p=0.010), and the area under the curve for γ-H2AX over 24 hours was markedly lower (p=0.014), signifying enhanced repair efficiency.
Post-exercise serum also increased PNKP expression – a key DNA repair gene – both with and without irradiation (p=0.007 and p=0.029, respectively).
RNA sequencing revealed extensive transcriptomic remodelling: 1,364 genes were differentially expressed, with upregulated pathways linked to mitochondrial energy metabolism, oxidative phosphorylation and protein synthesis. Downregulated pathways were associated with cell cycle progression and proteasome activity, consistent with a less proliferative state under genotoxic stress.
Proteomic profiling showed that acute exercise increased the abundance of 13 serum proteins involved in acute-phase immune signalling, vascular remodelling and oxidative stress responses (p<0.05).
Insights could lead to new colon cancer therapies
While the findings strengthen the rationale for integrating structured exercise into standard colon cancer care, several limitations were noted. The experiments used a single two-dimensional colon cancer cell line, which would not fully recognise the complexity of the tumour microenvironment. The exercise intervention was brief yet maximal, which may not be appropriate for all patient groups, and it was unclear whether lower-intensity exercise would produce comparable effects. Additionally, serum was collected from healthy, overweight/obese adults rather than from individuals with cancer, although prior evidence suggests similar acute molecular responses in people with cancer.
Despite these limitations, the findings strengthen the rationale for incorporating structured exercise into standard colon cancer care. Dr Sam Orange, senior lecturer in clinical exercise physiology at Newcastle University, who led the study, commented: ‘What’s remarkable is that exercise doesn’t just benefit healthy tissues, it sends powerful signals through the bloodstream that can directly influence thousands of genes in cancer cells.
‘It’s an exciting insight because it opens the door to find ways that mimic or augment the biological effects of exercise, potentially improving cancer treatment and, crucially, patient outcomes.
‘In the future, these insights could lead to new therapies that imitate the beneficial effects of exercise on how cells repair damaged DNA and use fuel for energy.’
Previous research has shown that good physical fitness combined with muscular strength could reduce cancer patient deaths.
Reference
Orange S et al. Exercise serum promotes DNA damage repair and remodels gene expression in colon cancer cells. Int J Cancer 2025;Dec 12:doi: 10.1002/ijc.70271.
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