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

Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:70

Enthalten in:

Redox biology - 70(2024) vom: 21. Feb., Seite 103033

Sprache:

Englisch

Beteiligte Personen:

Moulton, Chantalle [VerfasserIn]
Murri, Arianna [VerfasserIn]
Benotti, Gianmarco [VerfasserIn]
Fantini, Cristina [VerfasserIn]
Duranti, Guglielmo [VerfasserIn]
Ceci, Roberta [VerfasserIn]
Grazioli, Elisa [VerfasserIn]
Cerulli, Claudia [VerfasserIn]
Sgrò, Paolo [VerfasserIn]
Rossi, Cristina [VerfasserIn]
Magno, Stefano [VerfasserIn]
Di Luigi, Luigi [VerfasserIn]
Caporossi, Daniela [VerfasserIn]
Parisi, Attilio [VerfasserIn]
Dimauro, Ivan [VerfasserIn]

Links:

Volltext

Themen:

Antioxidants
Breast cancer
DNA methylation
EC 1.-
Epigenetic
Exercise
Journal Article
Mixed Function Oxygenases
Oxidative stress
Proto-Oncogene Proteins
RNA, Messenger
Redox-status
TET1 protein, human

Anmerkungen:

Date Completed 26.02.2024

Date Revised 26.02.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.redox.2024.103033

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM367019892