High intensity interval training as a therapy: Mitophagy restoration in breast cancer

Arch Biochem Biophys. 2024 Dec:762:110213. doi: 10.1016/j.abb.2024.110213. Epub 2024 Nov 7.

Abstract

Recent studies have highlighted the role of mitophagy in tumorigenesis. This study aimed to investigate the effects of high-intensity interval training (HIIT) on mitophagy in tumor tissues of mice with breast cancer. Twenty-eight female BALB/c mice were randomly assigned to four groups: Healthy Control (CO), Cancer (CA), Exercise (EX), and Cancer + Exercise (CA + EX). Mammary tumors were induced in the CA and CA + EX groups via 4T1 cell injections. Upon confirmation of tumor formation, the EX and CA + EX groups underwent 8 weeks (40 sessions) of HIIT, comprising 4-10 intervals of running at 80-100 % of maximum speed. The expression levels of mitophagy-related proteins, including parkin, PTEN-induced putative kinase 1 (PINK1), NIP3-like protein X (NIX), BCL2 interacting protein-3 (BINP3), microtubule-associated protein light chain 3-I (LC3-I), microtubule-associated protein light chain 3-II (LC3-II), AMP-activated protein kinase (AMPK), Unc-51 like autophagy activating kinase-1 (ULK1), and sirtuin-1 (SIRT1), were measured in breast and tumor tissues. Tumor volume relative to body weight was assessed weekly during the eight-week HIIT intervention. Protein expression of parkin, PINK1, NIX, BINP3, LC3-II, LC3-I, AMPK, ULK1, and SIRT1 was reduced in the breast tissue of the CA group, while HIIT restored expression levels across all measured variables (P < 0.01). Additionally, tumor volume relative to body weight was significantly lower in the CA + EX group compared to the CA group from weeks 3-8 (P < 0.01). These findings suggest that breast cancer suppresses mitophagy, yet HIIT effectively reverses this suppression, potentially reducing tumor burden. HIIT may thus represent a promising therapeutic strategy for managing breast cancer.

Keywords: Breast cancer; Exercise; Mitophagy; Tumor volume.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Autophagy-Related Protein-1 Homolog / metabolism
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Breast Neoplasms* / therapy
  • Cell Line, Tumor
  • Female
  • High-Intensity Interval Training*
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / pathology
  • Mammary Neoplasms, Experimental / therapy
  • Mice
  • Mice, Inbred BALB C*
  • Microtubule-Associated Proteins / metabolism
  • Mitophagy*
  • Physical Conditioning, Animal*
  • Protein Kinases / metabolism
  • Sirtuin 1 / metabolism
  • Ubiquitin-Protein Ligases* / metabolism

Substances

  • Ubiquitin-Protein Ligases
  • parkin protein
  • PTEN-induced putative kinase
  • Protein Kinases
  • Sirtuin 1
  • Microtubule-Associated Proteins
  • AMP-Activated Protein Kinases
  • Autophagy-Related Protein-1 Homolog