How intense workouts signal the bloodstream to suppress colorectal cancer genes

Researchers found that brief intense workouts enhance DNA repair in colon cancer cells by altering proteins circulating in the bloodstream

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A new study published in the International Journal of Cancer has found that even brief bouts of intense physical activity can trigger molecular changes in the body that may help suppress the growth of colorectal cancer cells and accelerate DNA repair mechanisms.

Researchers from Newcastle University in the UK report that just 10 minutes of high-intensity exercise can alter the composition of molecules circulating in the bloodstream. These exercise-induced signals appear to influence how cancer cells behave, slowing their growth, enhancing their ability to repair DNA damage, and shifting them towards a less aggressive state.

According to the World Health Organisation (WHO), colorectal cancer, also known as bowel cancer, is the second leading cause of cancer-related deaths globally. In 2020 alone, an estimated 1.9 million new cases and over 9.3 lakh deaths were recorded worldwide. Against this backdrop, the findings of the current study could open new avenues for understanding how physical activity plays a protective role against cancer, potentially strengthening the case for exercise as a complementary strategy in cancer prevention and care.

What the study found

The study helps explain one of the biological mechanisms through which exercise may protect against colorectal cancer, by sending powerful molecular signals through the bloodstream that directly influence the behaviour of cancer cells.

“Exercise protects against colon cancer progression, but the underlying biological mechanisms remain unclear,” the authors wrote. One proposed pathway, they explained, is the release of bioactive molecules into systemic circulation during exercise, which may act directly on tumour cells to suppress DNA damage, inhibit proliferation, and preserve genomic stability.

To explore this, the researchers examined how blood serum collected before and after acute exercise affected human colon cancer cells in laboratory conditions.

Blood samples were collected from 30 overweight or obese but otherwise healthy adults - men and women aged between 50 and 78, both before and immediately after a maximal incremental cycling test lasting approximately 10 to 12 minutes. Obesity is a known risk factor for colorectal cancer, making this group particularly relevant for the study.

The post-exercise blood serum was then applied to LoVo colon cancer cells in the lab. The cells were exposed to radiation-induced DNA damage and monitored over 24 hours to assess how efficiently they repaired this damage.

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The results were striking. Acute exercise significantly altered the circulating proteome - the complete set of proteins found in blood serum. Of the 249 proteins analysed, 13 showed a significant increase after exercise. These included interleukin-6 (IL-6) and its soluble receptor IL-6R, both of which are involved in immune activation, inflammation control, and vascular signalling.

When cancer cells were exposed to post-exercise serum, researchers observed a significant reduction in γ-H2AX foci - a marker of DNA damage, six hours after radiation exposure. This indicated faster and more efficient DNA repair compared to cells exposed to pre-exercise serum.

Post-exercise serum also increased the expression of a key DNA repair gene called PNKP, both with and without radiation exposure. Transcriptomic analysis revealed widespread gene expression changes: genes involved in mitochondrial energy metabolism were upregulated, while those linked to cell cycle progression and proteasome activity—processes associated with rapid cell growth—were downregulated.

In total, the activity of more than 1,300 genes was altered following exposure to exercise-conditioned serum, including genes governing DNA repair, energy production, and cancer cell proliferation.

"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,” said Dr Sam Orange, Senior Lecturer in Clinical Exercise Physiology at Newcastle University and lead author of the study.

“These findings suggest that acute exercise elicits systemic responses that enhance DNA repair and shift colon cancer cells towards a less proliferative transcriptomic state under sublethal genotoxic stress,” the authors noted, offering a potential mechanistic explanation for the protective effects of exercise against colorectal carcinogenesis.

The researchers also observed that exercise boosted mitochondrial efficiency, enabling cells to use oxygen more effectively, while simultaneously switching off genes associated with uncontrolled cell growth - changes that could reduce the aggressiveness of cancer cells.

"Even a single workout can make a difference. One bout of exercise, lasting just 10 minutes, sends powerful signals to the body. It's a reminder that every step, every session, counts when it comes to doing your best to protect your health,” Dr Orange said. 

Limitations of the study 

While the findings are promising, the researchers cautioned against overgeneralisation and acknowledged several limitations. Some limitations were methodological. “We used a single two-dimensional cell culture model, which does not capture the full complexity of tumour heterogeneity or the microenvironment,” the authors wrote. 

However, they added that genomic instability driven by persistent DNA damage is a hallmark of many cancers, suggesting that the observed effects may be relevant beyond this specific model.

The exercise protocol itself also raises questions about real-world applicability. The acute exercise trial involved maximal effort over a short duration, which “may not be feasible or appropriate for some individuals with cancer, particularly during active treatment or for those with co-morbidities.”

Because systemic responses to exercise are partly intensity-dependent, it remains unclear whether lower-intensity or moderate exercise would produce similar molecular effects. The authors noted that future studies should explore whether different forms and intensities of physical activity can elicit comparable biological responses.

Another limitation was the use of serum from healthy, overweight or obese individuals rather than cancer patients. According to the researchers, this decision was intentional, as the goal was to isolate the systemic molecular response to acute exercise, often referred to as the “exerkine response”, and test its direct effects on cancer cells in vitro.

Evidence suggests that people with obesity and people with cancer exhibit broadly similar acute molecular responses to exercise, including increases in IL-6, supporting the relevance of this experimental model.

Why it matters

The findings are particularly significant for India, where colorectal cancer is emerging as a growing public health concern. According to the World Cancer Research Fund, India recorded 70,038 new colorectal cancer cases in 2022, with an age-standardised incidence rate of 4.9 per 100,000 population. This means that roughly five out of every one lakh people developed colorectal cancer after accounting for age differences.

Out of approximately 1.92 million global cases, India ranked fifth, after China, the United States, Japan, and Russia.

Several Indian studies have highlighted the role of lifestyle factors, particularly physical inactivity, in increasing colorectal cancer risk. A 2017 hospital-based case–control study conducted in southern Karnataka examined 100 incident colorectal cancer patients and 200 unmatched controls. The researchers collected detailed information on sociodemographic factors, dietary habits, physical activity levels, substance use, co-morbidities, and family history of cancer.

On multivariable analysis, age above 50 years, low physical activity, low frequency of fruit consumption, and hypertension were all positively associated with colorectal cancer. Low physical activity showed one of the strongest associations, with an odds ratio of 5.66, indicating a significantly higher risk among inactive individuals.

The study concluded that “promoting healthy dietary practices and physical activity among the middle-aged population appears to be significant in the context of colorectal cancer prevention in the Indian subcontinent.”

Another study found a stark difference in exercise habits between colorectal cancer patients and healthy controls. Nearly 87.1 per cent of colorectal cancer cases reported no regular exercise, compared with 50 per cent among controls, suggesting a strong link between physical inactivity and colorectal cancer risk in the Indian population.

At a policy level, India has begun strengthening cancer prevention and care infrastructure. According to a recent reply in the Lok Sabha, the National Programme for Prevention and Control of Non-Communicable Diseases (NP-NCD) under the National Health Mission supports screening, early diagnosis, referral, treatment, and health promotion for cancers.

As of recent data, 770 District NCD Clinics, 364 District Day Care Cancer Centres, and over 6,400 NCD clinics at Community Health Centres have been established nationwide. Advanced cancer care is provided through 19 State Cancer Institutes and 20 Tertiary Cancer Care Centres, with diagnostic and treatment facilities approved across all new AIIMS institutions.

Specialised facilities such as the National Cancer Institute in Jhajjar and the Chittaranjan National Cancer Institute in Kolkata offer super specialty care, while additional cancer centres have been set up under the Department of Atomic Energy. The Union Budget 2025–26 further approved more than 200 new Day Care Cancer Centres across the country.

As part of its efforts to promote health and fitness, India launched the Fit India Movement in 2019. This initiative encourages citizens to adopt healthier lifestyles through regular exercise, yoga, and balanced diets, highlighting the importance of physical activity for overall well-being.

This story is done in collaboration with First Check, which is the health journalism vertical of DataLEADS.