Mitochondria-Targeted Antioxidant SkQ1 Improves Muscle Contractility in Female C26 Tumor-Bearing Mice
Authors: Tsitkanou Stavroula , Morena da Silva Francielly , Cabrera Regina , Schrems Eleanor , Koopmans Pieter , Khadgi Sabin , Jones Ronald , Lim Seongkyun , Washington Tyrone , Murach Kevin , Greene Nicholas 
Published: May 2023

Cancer cachexia (CC) affects up to 80% of cancer patients and is responsible for 20-40% of cancer related deaths. Our laboratory recently demonstrated that emission of muscle mitochondrial reactive oxygen species (ROS) is highly elevated shortly after the onset of tumor-bearing in mice. Therefore, targeting of mitochondrial ROS may be a viable option to treat and prevent CC. The aim of this study was to evaluate the effectiveness of a mitochondria-targeted antioxidant, SkQ1, at preventing CC. We hypothesized SkQ1 prevents muscle atrophy and weakness in tumor-bearing mice. To test the effect of SkQ1 on CC, female Balb/c mice were injected bilaterally with colon 26 adenocarcinoma (C26) cells to the hind flanks for a total cell volume of 1x106, while equal volume of PBS was injected in a separate cohort as a sham control. SkQ1 was dissolved in drinking water (250 nmol/kg body weight/day) and administered to mice, while control groups drank normal drinking water. Body weight was assessed every 5 days. In vivo muscle contractility and fatigability were assessed via electrophysiological measurements two days prior to endpoint. At the endpoint (~25 days after C26/PBS injections) body weight and tissue wet weights were measured and normalized by tibia length (mg/mm). Data were analyzed by 2X2 ANOVA with Tukey’s post hoc test where significant interactions were found with p≤0.05. C26 mice had lower tumor-free body weight (p<0.05), as well as the weights of gastrocnemius, tibialis anterior, extensor digitorum longus, quadriceps and heart (p<0.05), accompanied by increased liver and spleen weight (p<0.01) regardless of SkQ1 treatment. An interaction between C26 and SkQ1 was found in plantaris weight (p<0.01) with cancer mice treated by SkQ1 (C26 SkQ1) presenting lower plantaris weight compared to non-treated cancer mice (C26 CON): 0.788 vs. 0.874 mg/mm (p<0.05). The normalized (by tumor-free body weight) maximal isometric torque produced by C26 SkQ1 was higher compared to C26 CON: 0.078 vs 0.066 mN·m/gr (p<0.05). The normalized torques produced at frequencies 80-300 Hz were also higher in C26 SkQ1 compared to C26 CON (p<0.05). Muscle fatiguability was not affected by either cancer or SkQ1. In conclusion, the mitochondria-targeted antioxidant SkQ1 protects cancer-induced muscle weakness in female C26 tumor-bearing mice, although it may accelerate cancer-induced muscle wasting in some muscle groups. Data analysis is ongoing to clarify the effects of SkQ1 on cancer-induced cachexia in both male and female mice. This study was supported by the National Institutes of Health Award Number 5R01AR075794-02. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.