Most anticancer treatments act on oxidative-stress pathways by producing reactive oxygen species (ROS) to kill cancer cells, commonly resulting in consequential drug-induced systemic cytotoxicity. ...Physical activity (PA) has arisen as an integrative cancer therapy, having positive health effects, including in redox-homeostasis. Here, we investigated the impact of an online supervised PA program on promoter-specific DNA methylation, and corresponding gene expression/activity, in 3 antioxidants- (SOD1, SOD2, and CAT) and 3 breast cancer (BC)-related genes (BRCA1, L3MBTL1 and RASSF1A) in a population-based sample of women diagnosed with primary BC, undergoing medical treatment. We further examined mechanisms involved in methylating and demethylating pathways, predicted biological pathways and interactions of exercise-modulated molecules, and the functional relevance of modulated antioxidant markers on parameters related to aerobic capacity/endurance, physical fatigue and quality of life (QoL).
PA maintained levels of SOD activity in blood plasma, and at the cellular level significantly increased SOD2 mRNA (≈+77 %), contrary to their depletion due to medical treatment. This change was inversely correlated with DNA methylation in SOD2 promoter (≈−20 %). Similarly, we found a significant effect of PA only on L3MBTL1 promoter methylation (≈−25 %), which was inversely correlated with its mRNA (≈+43 %). Finally, PA increased TET1 mRNA levels (≈+15 %) and decreased expression of DNMT3B mRNA (≈−28 %).
Our results suggest that PA-modulated DNA methylation affects several signalling pathways/biological activities involved in the cellular oxidative stress response, chromatin organization/regulation, antioxidant activity and DNA/protein binding. These changes may positively impact clinical outcomes and improve the response to cancer treatment in post-surgery BC patients.
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•Physical activity prevents antioxidants depletion during cancer treatment.•Antioxidant gene-specific methylation is modulated by physical activity.•Antioxidant marker changes predict variable of distress symptom outcomes.
Breast cancer (BC) is one of the most commonly diagnosed types of cancer in women. Oxidative stress may contribute to cancer etiology through several mechanisms. A large body of evidence indicates ...that physical activity (PA) has positive effects on different aspects of BC evolution, including mitigation of negative effects induced by medical treatment. With the aim to verify the capacity of PA to counteract negative effects of BC treatment on systemic redox homeostasis in postsurgery female BC patients, we have examined the modulation of circulating levels of oxidative stress and inflammation markers. Moreover, we evaluated the impacts on physical fitness and mental well-being by measuring functional parameters, body mass index, body composition, health-related quality of life (QoL), and fatigue. Our investigation revealed that PA was effective in maintaining plasma levels of superoxide dismutase (SOD) activity and tGSH, as well as peripheral blood mononuclear cells' (PBMCs) mRNA levels of SOD1 and heat-shock protein 27. Moreover, we found a significant decrease in plasma interleukin-6 (≈0.57 ± 0.23-fold change,
< 0.05) and increases in both interleukin-10 (≈1.15 ± 0.35-fold change,
< 0.05) and PBMCs' mRNA level of SOD2 (≈1.87 ± 0.36-fold change,
< 0.05). Finally, PA improves functional parameters (6 min walking test, ≈+6.50%,
< 0.01; Borg, ≈-58.18%,
< 0.01; sit-and-reach, ≈+250.00%,
< 0.01; scratch right, ≈-24.12%, and left, ≈-18.81%,
< 0.01) and body composition (free fat mass, ≈+2.80%,
< 0.05; fat mass, ≈-6.93%,
< 0.05) as well as the QoL (physical function, ≈+5.78%,
< 0.05) and fatigue (cognitive fatigue, ≈-60%,
< 0.05) parameters. These results suggest that a specific PA program not only is effective in improving functional and anthropometric parameters but may also activate cellular responses through a multitude of actions in postsurgery BC patients undergoing adjuvant therapy. These may include modulation of gene expression and protein activity and impacting several signaling pathways/biological activities involved in tumor-cell growth; metastasis; and inflammation, as well as moderating distress symptoms known to negatively affect QoL.
Considering the role of redox homeostasis in exercise-induced signaling and adaptation, this study focuses on the exercise training-related intercellular communication of redox status mediated by ...circulating extracellular vesicles (EVs).
19 healthy young males were divided into trained (TG, 7) and untrained (UG, 12) subjects based on their VO2MAX. The UG subjects were further randomly distributed in experimental (UGEX, N = 7) and control (UGCTRL, N = 5) groups. The steady state of plasma EVs in TG and UGEX have been characterized for total number and size, as well as cargo redox status (antioxidants, transcription factors, HSPs) before, 3 and 24 h after a single bout of aerobic exercise (30’, 70% HRM). Plasma EVs from UGEX and UGCTRL have been further characterized after 24 h from the last session of a 5-day consecutive aerobic training or no training, respectively.
No differences were detected in the EVs’ size and distribution at baseline in TG and UGEX (p>0.05), while the EVs cargo of UGEX showed a significantly higher concentration of protein carbonyl, Catalase, SOD2, and HSF1 compared to TG (p<0.05). 5 days of consecutive aerobic training in UGEX did not determine major changes in the steady-state number and size of EVs. The post-training levels of protein carbonyl, HSF1, Catalase, and SOD2 in EVs cargo of UGEX resulted significantly lower compared with UGEX before training and UGCTRL, resembling the steady-state levels in circulating EVs of TG subjects.
Altogether, these preliminary data indicate that individual aerobic capacity influences the redox status of circulating EVs, and that short-term aerobic training impacts the steady-state redox status of EVs. Taking this pilot study as a paradigm for physio-pathological stimuli impacting redox homeostasis, our results offer new insights into the utilization of circulating EVs as biomarkers of exercise efficacy and of early impairment of oxidative-stress related diseases.
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•Regular participation to structured sport activity improves the redox homeostasis of circulating extracellular vesicles (EVs).•5 days of consecutive aerobic training in untrained subjects determines the improvement of redox homeostasis in EVs cargo.•These preliminary results identify plasma EVs as promising biomarkers of the individual early response to the exercise intervention.
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