Oncotarget: Preventing colon 26 cancer-induced cardiorespiratory muscle weakness

 Oncotarget recently published "Pharmacological targeting of mitochondrial function and reactive oxygen species production prevents colon 26 cancer-induced cardiorespiratory muscle weakness" which reported, that to determine if pharmacologically targeting mitochondrial dysfunction via treatment with the mitochondria-targeting peptide SS-31 would prevent cardiorespiratory muscle dysfunction, colon 26 adenocarcinoma tumor-bearing mice were administered either saline or SS-31 daily following inoculation.

C26 mice treated with saline demonstrated greater ROS production and mitochondrial uncoupling compared to C26 mice receiving SS-31 in both the heart and diaphragm muscle.

In addition, saline-treated C26 mice exhibited a decline in left ventricular function which was significantly rescued in C26 mice treated with SS-31. In the diaphragm, muscle fiber cross-sectional area of C26 mice treated with saline was significantly reduced and force production was impaired compared to C26, SS-31-treated animals.

Finally, ventilatory deficits were also attenuated in C26 mice treated with SS-31, compared to saline treatment.

These data demonstrate that C26 tumors promote severe cardiac and respiratory myopathy, and that prevention of mitochondrial dysfunction is sufficient to preclude cancer cachexia-induced cardiorespiratory dysfunction.

Dr. Ashley J. Smuder from The University of Florida said, "Cachexia is a debilitating consequence of cancer, most prevalent in patients with gastrointestinal, pancreatic, lung and colorectal cancers."

The Oncotarget authors indicated that, indeed, body weight loss in individuals with cancer cachexia is accompanied by cardiac muscle wasting and significant inspiratory muscle weakness, which often present initially as fatigue, shortness of breath and exercise intolerance, but can compromise survival by advancing into ventilatory and/or heart failure.

In fact, impaired mitochondrial function was demonstrated to precede the development of cachexia in Lewis lung carcinoma tumor-bearing mice, which supports the premise that mitochondrial dysfunction may be critical to the development of cancer cachexia.