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Integrated mitochondrial function and cancer-related fatigue in men with prostate cancer undergoing radiation therapy

Authors Hsiao CP, Chen MK, Daly B, Hoppel C

Received 31 August 2018

Accepted for publication 4 November 2018

Published 26 November 2018 Volume 2018:10 Pages 6367—6377

DOI https://doi.org/10.2147/CMAR.S185706

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Andrew Yee

Peer reviewer comments 2

Editor who approved publication: Professor Nakshatri


Chao-Pin Hsiao,1 Mei-Kuang Chen,2 Barbara Daly,1 Charles Hoppel3

1Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH, USA; 2Department of Psychology, University of Arizona, Tucson, AZ, USA; 3Center for Mitochondrial Disease, Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA

Introduction: Fatigue experienced by cancer patients is one of the most common symptoms with the greatest adverse effect on quality of life, but arguably the least understood. The purpose of this study was to explore changes in integrated mitochondrial function and fatigue in non-metastatic prostate cancer patients receiving localized radiation therapy (XRT).
Materials and methods: We proposed a mitochondrial bioenergetics mechanism of radiation-induced fatigue linking impaired oxidative phosphorylation (OXPHOS) through complex III and decreased adenosine triphosphate (ATP) production as consequences of XRT. Integrated mitochondrial function was measured as mitochondrial OXPHOS from patients’ peripheral blood mononuclear cells. Fatigue was measured using the revised Piper Fatigue Scale. Data were collected before (day 0) and at day 21 of XRT.
Results: At day 21 of XRT, fatigue symptom intensified in 15 prostate cancer patients (P<0.05). Mitochondrial OXPHOS complex III-linked and uncoupled complex III rates were significantly decreased in mononuclear cells at day 21 during XRT compared to that before XRT (P<0.05). Additionally, increased fatigue appeared to be associated with decreased OXPHOS complex III-linked respiration in patients undergoing XRT.
Conclusion: Fatigue was associated with OXPHOS complex III-linked oxidation and a defect in oxidation starting at complex III in mononuclear cell mitochondria was revealed at day 21 of XRT in 15 prostate cancer patients. Complex III is a potential target for pharmacological and, in particular, nutraceutical interventions, eg, Q10, for design of interventions for CRF.

Keywords: integrated mitochondrial function, oxidative phosphorylation, cancer-related fatigue, radiation therapy, prostate cancer

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