Peripheral blood mononuclear cells exhibit increased mitochondrial respiration after adjuvant chemo- and radiotherapy for early breast cancer

4Citations
Citations of this article
6Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Background: Adjuvant chemo- and radiotherapy cause cellular damage to tumorous and healthy dividing cells. Chemotherapy has been shown to cause mitochondrial respiratory dysfunction in non-tumorous tissues, but the effects on human peripheral blood mononuclear cells (PBMCs) remain unknown. Aim: We aimed to investigate mitochondrial respiration of PBMCs before and after adjuvant chemo- and radiotherapy in postmenopausal patients with early breast cancer (EBC) and relate these to metabolic parameters of the patients. Methods: Twenty-three postmenopausal women diagnosed with EBC were examined before and shortly after chemotherapy with (n = 18) or without (n = 5) radiotherapy. Respiration (O2 flux per million PBMCs) was assessed by high-resolution respirometry of intact and permeabilized PBMCs. Clinical metabolic characteristics and mitochondrial DNA (mtDNA) content of PBMCs (mtDN relative to nuclear DNA) were furthermore assessed. Results: Respiration of intact and permeabilized PBMCs from EBC patients significantly increased with adjuvant chemo- and radiotherapy (p = 6 × 10−5 and p = 1 × 10−7, respectively). The oxygen flux attributed to specific mitochondrial complexes and respiratory states increased by 17–43% compared to before therapy initiation. Similarly, PBMC mtDNA content increased by 40% (p = 0.002). Leukocytes (p = 0.0001), hemoglobin (p = 0.0003), and HDL cholesterol (p = 0.003) concentrations decreased whereas triglyceride (p = 0.01) and LDL (p = 0.02) concentrations increased after treatment suggesting a worsened metabolic state. None of the metabolic parameters or the mtDNA content of PBMCs correlated significantly with PBMC respiration. Conclusion: This study shows that mitochondrial respiration and mtDNA content in circulating PBMCs increase after adjuvant chemo- and radiotherapy in postmenopausal patients with EBC. Besides the increased mtDNA content, a shift in PBMC subpopulation proportions towards cells relying on oxidative phosphorylation, who may be less sensitive to chemotherapy, might influence the increased mitochondrial respiration observed iafter chemotherapy.

References Powered by Scopus

Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

70124Citations
N/AReaders
Get full text

Cancer statistics, 2020

16438Citations
N/AReaders
Get full text

Risk of ischemic heart disease in women after radiotherapy for breast cancer

3023Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Arsenic trioxide augments immunogenic cell death and induces cGAS-STING-IFN pathway activation in hepatocellular carcinoma

4Citations
N/AReaders
Get full text

Exercise training alters skeletal muscle microvascular endothelial cell properties in recent postmenopausal females

2Citations
N/AReaders
Get full text

Pro-inflammatory cytokines increase temporarily after adjuvant treatment for breast cancer in postmenopausal women: a longitudinal study

0Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Christensen, I. B., Abrahamsen, M. L., Ribas, L., Buch-Larsen, K., Marina, D., Andersson, M., … Gillberg, L. (2023). Peripheral blood mononuclear cells exhibit increased mitochondrial respiration after adjuvant chemo- and radiotherapy for early breast cancer. Cancer Medicine, 12(16), 16985–16996. https://doi.org/10.1002/cam4.6333

Readers' Seniority

Tooltip

Researcher 2

100%

Readers' Discipline

Tooltip

Agricultural and Biological Sciences 1

33%

Biochemistry, Genetics and Molecular Bi... 1

33%

Medicine and Dentistry 1

33%

Save time finding and organizing research with Mendeley

Sign up for free