Abstract

Both regular exercise training and vitamin D consumption are beneficial for patients with cancer. The study investigated the effects of interval exercise training (IET) or/and vitamin D supplementation on the gene expression involved in mitochondrial function of heart tissue, tumor size, and total antioxidant capacity (TAC) in breast cancer (BC) model mice. We assigned random 40 female NMRI mice to five equal groups (n = 8); the healthy control group (H.C), cancer control group (Ca.C), cancer with the vitamin D group (Ca.VD), cancer exercise group (Ca.Ex), and cancer exercise along with the vitamin D group (Ca.Ex.VD). Forty-eight hours after treatment, we anesthetized the animals and performed the isolation of heart tissue and blood serum for further studies. The results showed that the lowest mean body weight at the end of the treatments was related to Ca.C (p = 0.001). Vitamin D treatment alone has increased tumor volume growth by approximately 23%; in contrast, co-treatment with exercise and vitamin D inhibited tumor growth in mice (P = 0.001), compared with the cancer control (12%). TAC levels were higher in the group that received both vitamin D and exercise training (Ca.Ex.VD) than in the other treatment groups (Ca.VD and Ca.Ex) (p = 0.001). In cardiac tissue, vitamin D treatment induces an elevation significantly of the mRNA expression of Pgc1−α, Mfn-1, and Drp-1 genes (p = 0.001). The study has shown the overexpression of vitamin D in female mice, and synergistic effects of IET with vitamin D on weight loss controlling, antitumorigenesis, improvement of antioxidant defense, and the modulation of gene expression. The synergistic responses were likely by increasing mitochondrial fusion and TAC to control oxidative stress. We recommended being conducted further studies on mitochondrial dynamics and biogenesis focusing on risk factors of cardiovascular disease (CVD) in patients with BC.

Highlights

  • Female breast cancer (BC) has outstripped lung cancer as the most generally detected cancer, with an assessed 2.3 million new cases (11.7%), followed by lung (11.4%) and other cancers in 2020 (Sung et al, 2021)

  • Peroxisome proliferator-activated receptor γ coactivator-1 (PGC1) is one of the genes involved in mitochondrial function which regulates numerous transcription factors responsible for energy metabolism and cardiac function, controlling mitochondrial biogenesis and dynamics, and modulating reactive oxygen species (ROS) homeostasis under physiological and pathological conditions

  • Given with reports associated with the contradictory role(s) of levels of PGC1α expression linked to carcinogenesis in the early stage, and elevating tumor cell phenotype in the late stage (Mastropasqua et al, 2018), we derive that PGC1α is neither friend nor foe in cancers; due to importance of mitochondrial function for heart health and the controversial role(s) of PGC1α, antioxidant status, and cardioprotective effect of vitamin D, it is warranted to investigate PGC1α as considered main regulators of mitochondrial biogenesis and quality, and antioxidant potential effects in cardioprotection following interval exercise training (IET) along with vitamin D intake in BC

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Summary

INTRODUCTION

Female breast cancer (BC) has outstripped lung cancer as the most generally detected cancer, with an assessed 2.3 million new cases (11.7%), followed by lung (11.4%) and other cancers in 2020 (Sung et al, 2021). Given with reports associated with the contradictory role(s) of levels of PGC1α expression linked to carcinogenesis in the early stage, and elevating tumor cell phenotype in the late stage (Mastropasqua et al, 2018), we derive that PGC1α is neither friend nor foe in cancers; due to importance of mitochondrial function for heart health and the controversial role(s) of PGC1α, antioxidant status, and cardioprotective effect of vitamin D, it is warranted to investigate PGC1α as considered main regulators of mitochondrial biogenesis and quality, and antioxidant potential effects in cardioprotection following interval exercise training (IET) along with vitamin D intake in BC. We characterize the impact of IET and vitamin D supplementation, a safe strategy against BC and CVD, on cardiac and its contribution to mitochondrial quality control, biogenesis, and total antioxidant capacity (TAC) in a post-tumorigenesis animal model

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