Mitochondrial Dysfunction is Evident in Lewis Lung Carcinoma-Induced Muscle Wasting

Authors

Conner Benson, University of Texas at TylerFollow
David E. Lee, University of Arkansas
Nicholas P. Greene, University of Arkansas
Jacob L. Brown, University of Arkansas
Megan E. Rosa, University of Arkansas
Tyrone A. Washington, University of Arkansas
Michael P. Wiggs, University of Texas at TylerFollow

Abstract

Cancer cachexia is a paraneoplastic syndrome associated with adverse prognosis and shortened survival. The defining feature of cachexia is extensive muscle atrophy leading to progressive functional impairments. The molecular mechanisms responsible for the rapid muscle wasting are not fully elucidated. Based on emerging evidence, we developed the hypothesis cachectic muscle wasting is caused by mitochondrial dysfunction increasing reactive oxygen species production leading to global oxidative stress. To test this hypothesis we utilized the well-established Lewis-Lung Carcinoma (LLC) model of cancer cachexia. The time-course study consisted of one, two, three and four week LLC tumor bearing mice and age-matched four week saline (PBS) control (Ctrl) mice. Tumors were implanted into the hind flank at 1X10⁶ cells in 100 µL PBS. The plantaris was weighed for wet mass then teased into small fiber bundles and permeabilized for the quantification of mitochondrial function. Mitochondrial dysfunction was classified by a decrease in the respiratory control ratio (RCR), which is the ratio of state 3 (maximal ADP stimulated respiration) to state 4 (oligomycin-induced leak respiration). Muscle mass progressively declined over the time-course, reaching significance at 4 weeks (Ctrl vs 4-week, p<0.05). Mitochondrial function was not different among groups, however individual a priori comparison between groups revealed that 4wk cancer animals exhibited marked mitochondrial dysfunction compared to all other groups (p<0.05). These data demonstrate that late stage cancer-induced muscle wasting is associated with significant mitochondrial dysfunction.

Recommended Citation

Benson, Conner; Lee, David E.; Greene, Nicholas P.; Brown, Jacob L.; Rosa, Megan E.; Washington, Tyrone A.; and Wiggs, Michael P. (2016) "Mitochondrial Dysfunction is Evident in Lewis Lung Carcinoma-Induced Muscle Wasting," International Journal of Exercise Science: Conference Proceedings: Vol. 2: Iss. 8, Article 110.
Available at: https://digitalcommons.wku.edu/ijesab/vol2/iss8/110