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

Abstract

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 mitochondria' bioenergetics mechanism of radiation-induced fatigue linking impaired oxidative phosphorylation (OXPIIOS) through complex III and decreased adenosine triphosphate (ATP) production as consequences of XRT. Integrated mitochondria' function was measured as mitochondria' 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 Ill-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.