Pharmacological targeting of mitochondrial function and reactive oxygen species production prevents colon 26 cancer-induced cardiorespiratory muscle weakness.

Smuder AJ, Roberts BM, Wiggs MP, Kwon OS, Yoo JK, Christou DD, Fuller DD, Szeto HH, Judge AR

Oncotarget22 Sept 2020Cited by 31 (Europe PMC)

PMID33014286PMCIDPMC7517961DOI10.18632/oncotarget.27748PepBankPUB-33014286

Summary

Cancer cachexia is a syndrome characterized by profound cardiac and diaphragm muscle wasting, which increase the risk of morbidity in cancer patients due to failure of the cardiorespiratory system. In this regard, muscle relies greatly on mitochondria to meet energy requirements for contraction and mitochondrial dysfunction can result in muscle weakness and fatigue. In addition, mitochondria are a major source of reactive oxygen species (ROS) production, which can stimulate increased rates of muscle protein degradation. Therefore, it has been suggested that mitochondrial dysfunction may be an underlying factor that contributes to the pathology of cancer cachexia. To determine if pharmacologically targeting mitochondrial dysfunction via treatment with the mitochondria-targeting peptide SS-31 would prevent cardiorespiratory muscle dysfunction, colon 26 (C26) adenocarcinoma tumor-bearing mice were administered either saline or SS-31 daily (3 mg/kg/day) 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.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

6 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Mechanism
In C26 tumor-bearing mice, SS‑31 lowered ROS production in the heart and diaphragm compared with saline.
In plain wordsIn mice with colon tumors, SS‑31 lowered reactive oxygen species in the heart and diaphragm compared with saline.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseROS production in heart and diaphragm
Study
mousen: not reported in source
Colon 26 (C26) adenocarcinoma tumor-bearing mice
Comparator
Saline
Outcome group
Mitochondrial function · Cardiovascular
Studied dose
3 mg/kg/dayAs given in this study (mouse).
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
To determine if pharmacologically targeting mitochondrial dysfunction via treatment with the mitochondria-targeting peptide SS-31 would prevent cardiorespiratory muscle dysfunction, colon 26 (C26) adenocarcinoma tumor-bearing mice were administered either saline or SS-31 daily (3 mg/kg/day) following inoculation.
Show in the study text Report a problemFND-3301428601
02AnimalAnimal study (in vivo)Mechanism
In C26 tumor-bearing mice, SS‑31 lowered mitochondrial uncoupling in the heart and diaphragm compared with saline.
In plain wordsIn mice with colon tumors, SS‑31 reduced mitochondrial uncoupling in the heart and diaphragm compared with saline.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseMitochondrial uncoupling in heart and diaphragm
Study
mousen: not reported in source
Colon 26 (C26) adenocarcinoma tumor-bearing mice
Comparator
Saline
Outcome group
Mitochondrial function · Cardiovascular
Studied dose
3 mg/kg/dayAs given in this study (mouse).
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
To determine if pharmacologically targeting mitochondrial dysfunction via treatment with the mitochondria-targeting peptide SS-31 would prevent cardiorespiratory muscle dysfunction, colon 26 (C26) adenocarcinoma tumor-bearing mice were administered either saline or SS-31 daily (3 mg/kg/day) following inoculation.
Show in the study text Report a problemFND-3301428602
03AnimalAnimal study (in vivo)Efficacy outcome
In C26 tumor-bearing mice, SS‑31 significantly rescued the decline in left ventricular function seen with saline.
In plain wordsIn mice with colon tumors, SS‑31 rescued a decline in heart function seen with saline.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseLeft ventricular function
Study
mousen: not reported in source
Colon 26 (C26) adenocarcinoma tumor-bearing mice
Comparator
Saline
Outcome group
Heart function · Cardiovascular
Studied dose
3 mg/kg/dayAs given in this study (mouse).
Source sentences
Summary
In addition, saline-treated C26 mice exhibited a decline in left ventricular function which was significantly rescued in C26 mice treated with SS-31.
1 context sentence(design, population, supporting numbers)
Summary · context
To determine if pharmacologically targeting mitochondrial dysfunction via treatment with the mitochondria-targeting peptide SS-31 would prevent cardiorespiratory muscle dysfunction, colon 26 (C26) adenocarcinoma tumor-bearing mice were administered either saline or SS-31 daily (3 mg/kg/day) following inoculation.
Show in the study text Report a problemFND-3301428603
04AnimalAnimal study (in vivo)Efficacy outcome
In C26 tumor-bearing mice, diaphragm muscle fiber cross-sectional area was larger with SS‑31 than with saline.
In plain wordsIn mice with colon tumors, SS‑31 preserved diaphragm muscle fiber size compared with saline.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseDiaphragm muscle fiber cross-sectional area
Study
mousen: not reported in source
Colon 26 (C26) adenocarcinoma tumor-bearing mice
Comparator
Saline
Outcome group
Muscle injury and repair · Musculoskeletal
Studied dose
3 mg/kg/dayAs given in this study (mouse).
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
To determine if pharmacologically targeting mitochondrial dysfunction via treatment with the mitochondria-targeting peptide SS-31 would prevent cardiorespiratory muscle dysfunction, colon 26 (C26) adenocarcinoma tumor-bearing mice were administered either saline or SS-31 daily (3 mg/kg/day) following inoculation.
Show in the study text Report a problemFND-3301428604
05AnimalAnimal study (in vivo)Efficacy outcome
In C26 tumor-bearing mice, diaphragm force production was higher with SS‑31 than with saline.
In plain wordsIn mice with colon tumors, SS‑31 preserved diaphragm muscle force compared with saline.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseDiaphragm force production
Study
mousen: not reported in source
Colon 26 (C26) adenocarcinoma tumor-bearing mice
Comparator
Saline
Outcome group
Exercise and physical function · Musculoskeletal
Studied dose
3 mg/kg/dayAs given in this study (mouse).
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
To determine if pharmacologically targeting mitochondrial dysfunction via treatment with the mitochondria-targeting peptide SS-31 would prevent cardiorespiratory muscle dysfunction, colon 26 (C26) adenocarcinoma tumor-bearing mice were administered either saline or SS-31 daily (3 mg/kg/day) following inoculation.
Show in the study text Report a problemFND-3301428605
06AnimalAnimal study (in vivo)Efficacy outcome
In C26 tumor-bearing mice, SS‑31 attenuated ventilatory deficits compared with saline.
In plain wordsIn mice with colon tumors, SS‑31 reduced breathing deficits compared with saline.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseVentilatory deficits
Study
mousen: not reported in source
Colon 26 (C26) adenocarcinoma tumor-bearing mice
Comparator
Saline
Outcome group
Respiratory function · Respiratory
Studied dose
3 mg/kg/dayAs given in this study (mouse).
Source sentences
Summary
Finally, ventilatory deficits were also attenuated in C26 mice treated with SS-31, compared to saline treatment.
1 context sentence(design, population, supporting numbers)
Summary · context
To determine if pharmacologically targeting mitochondrial dysfunction via treatment with the mitochondria-targeting peptide SS-31 would prevent cardiorespiratory muscle dysfunction, colon 26 (C26) adenocarcinoma tumor-bearing mice were administered either saline or SS-31 daily (3 mg/kg/day) following inoculation.
Show in the study text Report a problemFND-3301428606

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
10 Oct 2026, 08:19 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

Subjects

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Keywords

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