Anthracycline-containing chemotherapy causes long-term impairment of mitochondrial respiration and increased reactive oxygen species release in skeletal muscle

Scientific Reports
Gilles GouspillouR Thomas Jagoe

Abstract

Anticancer treatments for childhood acute lymphoblastic leukaemia (ALL) are highly effective but are now implicated in causing impaired muscle function in long-term survivors. However, no comprehensive assessment of skeletal muscle mitochondrial functions in long-term survivors has been performed and the presence of persistent chemotherapy-induced skeletal muscle mitochondrial dysfunction remains a strong possibility. Non-tumour-bearing mice were treated with two drugs that have been used frequently in ALL treatment (doxorubicin and dexamethasone) for up to 4 cycles at 3-week intervals and euthanized 3 months after the 4th cycle. Treated animals had impaired growth and lower muscle mass as well as reduced mitochondrial respiration and increased reactive oxygen species production per unit oxygen consumption. Mitochondrial DNA content and protein levels of key mitochondrial membrane proteins and markers of mitochondrial biogenesis were unchanged, but protein levels of Parkin were reduced. This suggests a novel pattern of chemotherapy-induced mitochondrial dysfunction in skeletal muscle that persists because of an acquired defect in mitophagy signaling. The results could explain the observed functional impairments in adult survivo...Continue Reading

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Citations

May 12, 2016·Cancer Chemotherapy and Pharmacology·James C SorensenEmma Rybalka
Oct 22, 2016·Frontiers in Physiology·Gilles Gouspillou, Russell T Hepple
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Apr 20, 2021·Journal of the National Cancer Institute·Kelly McCastlainKirsten K Ness
Jul 25, 2021·Cancers·Dean G CampeljEmma Rybalka

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Methods Mentioned

BETA
PCR
biopsies

Software Mentioned

Igor Pro
ImageJ

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