The impact of physical activity on promoter-specific methylation of genes involved in the redox-status and disease progression: A longitudinal study on post-surgery female breast cancer patients undergoing medical treatment
Chantalle Moulton,
Arianna Murri,
Gianmarco Benotti,
Cristina Fantini,
Guglielmo Duranti,
Roberta Ceci,
Elisa Grazioli,
Claudia Cerulli,
Paolo Sgrò,
Cristina Rossi,
Stefano Magno,
Luigi Di Luigi,
Daniela Caporossi,
Attilio Parisi,
Ivan Dimauro
Affiliations
Chantalle Moulton
Unit of Biology and Genetics of Movement, Department of Movement, Human and Health Sciences, University of Rome Foro Italico, Rome, Italy
Arianna Murri
Unit of Physical Exercise and Sport Sciences, Department of Movement, Human and Health Sciences, University of Rome Foro Italico, Rome, Italy
Gianmarco Benotti
Unit of Biology and Genetics of Movement, Department of Movement, Human and Health Sciences, University of Rome Foro Italico, Rome, Italy
Cristina Fantini
Unit of Biology and Genetics of Movement, Department of Movement, Human and Health Sciences, University of Rome Foro Italico, Rome, Italy
Guglielmo Duranti
Unit of Biochemistry and Molecular Biology, Department of Movement, Human and Health Sciences, University of Rome Foro Italico, Rome, Italy
Roberta Ceci
Unit of Biochemistry and Molecular Biology, Department of Movement, Human and Health Sciences, University of Rome Foro Italico, Rome, Italy
Elisa Grazioli
Unit of Physical Exercise and Sport Sciences, Department of Movement, Human and Health Sciences, University of Rome Foro Italico, Rome, Italy
Claudia Cerulli
Unit of Biochemistry and Molecular Biology, Department of Movement, Human and Health Sciences, University of Rome Foro Italico, Rome, Italy
Paolo Sgrò
Unit of Endocrinology, Department of Movement, Human and Health Sciences, University of Rome Foro Italico, Rome, Italy
Cristina Rossi
Center for Integrative Oncology, Fondazione Policlinico Universitario A.Gemelli IRCCS, Italy
Stefano Magno
Center for Integrative Oncology, Fondazione Policlinico Universitario A.Gemelli IRCCS, Italy
Luigi Di Luigi
Unit of Endocrinology, Department of Movement, Human and Health Sciences, University of Rome Foro Italico, Rome, Italy
Daniela Caporossi
Unit of Biology and Genetics of Movement, Department of Movement, Human and Health Sciences, University of Rome Foro Italico, Rome, Italy
Attilio Parisi
Unit of Physical Exercise and Sport Sciences, Department of Movement, Human and Health Sciences, University of Rome Foro Italico, Rome, Italy
Ivan Dimauro
Unit of Biology and Genetics of Movement, Department of Movement, Human and Health Sciences, University of Rome Foro Italico, Rome, Italy; Corresponding author.
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.
