Colon 26 adenocarcinoma (C26)-induced cancer cachexia impairs skeletal muscle mitochondrial function and content

Abstract

The present study aimed to determine the impact of colon 26 adenocarcinoma (C26)-induced cancer cachexia on skeletal muscle mitochondrial respiration and content. Twelve male CD2F1 mice were injected with C26-cells (tumor bearing (TB) group), whereas 12 age-matched mice received PBS vehicle injection (non-tumor bearing (N-TB) group). Mitochondrial respiration was studied in saponin-permeabilized soleus myofibers. TB mice showed lower body weight (~\u200920%) as well as lower soleus, gastrocnemius-plantaris complex and tibialis anterior masses versus N-TB mice (p\u2009<\u20090.05). Soleus maximal state III mitochondrial respiration was 20% lower (10\xa0mM glutamate, 5\xa0mM malate, 5\xa0mM adenosine diphosphate; p\u2009<\u20090.05) and acceptor control ratio (state III/state II) was 15% lower in the TB vs. N-TB (p\u2009<\u20090.05), with the latter suggesting uncoupling. Lower VDAC protein content suggested reduced mitochondrial content in TB versus N-TB (p\u2009<\u20090.05). Skeletal muscle in C26-induced cancer cachexia exhibits reductions in: maximal mitochondrial respiration capacity, mitochondrial coupling and mitochondrial content.