Targeting Mitochondria by SS-31 Ameliorates the Whole Body Energy Status in Cancer- and Chemotherapy-Induced Cachexia.

Ballarò R, Lopalco P, Audrito V, Beltrà M, Pin F, Angelini R, Costelli P, Corcelli A, Bonetto A, Szeto HH, O'Connell TM, Penna F

Cancers18 Feb 2021Cited by 48 (Europe PMC)

PMID33670497PMCIDPMC7923037DOI10.3390/cancers13040850PepBankPUB-33670497

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Summary

Objective: Cachexia is a complex metabolic syndrome frequently occurring in cancer patients and exacerbated by chemotherapy. In skeletal muscle of cancer hosts, reduced oxidative capacity and low intracellular ATP resulting from abnormal mitochondrial function were described. Methods: The present study aimed at evaluating the ability of the mitochondria-targeted compound SS-31 to counteract muscle wasting and altered metabolism in C26-bearing (C26) mice either receiving chemotherapy (OXFU: oxaliplatin plus 5-fluorouracil) or not. Results: Mitochondrial dysfunction in C26-bearing (C26) mice associated with alterations of cardiolipin fatty acid chains. Selectively targeting cardiolipin with SS-31 partially counteracted body wasting and prevented the reduction of glycolytic myofiber area. SS-31 prompted muscle mitochondrial succinate dehydrogenase (SDH) activity and rescued intracellular ATP levels, although it was unable to counteract mitochondrial protein loss. Progressively increased dosing of SS-31 to C26 OXFU mice showed transient (21 days) beneficial effects on body and muscle weight loss before the onset of a refractory end-stage condition (28 days). At day 21, SS-31 prevented mitochondrial loss and abnormal autophagy/mitophagy. Skeletal muscle, liver and plasma metabolomes were analyzed, showing marked energy and protein metabolism alterations in tumor hosts. SS-31 partially modulated skeletal muscle and liver metabolome, likely reflecting an improved systemic energy homeostasis. Conclusions: The results suggest that targeting mitochondrial function may be as important as targeting protein anabolism/catabolism for the prevention of cancer cachexia. With this in mind, prospective multi-modal therapies including SS-31 are warranted.

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

Results from this study9

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

01AnimalAnimal study (in vivo)Efficacy outcome
In C26 tumor-bearing mice, SS‑31 partially counteracted body wasting.
In plain wordsIn mice with cancer cachexia, SS‑31 partly reduced body wasting.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseBody wasting in C26 mice
Study
mousen: not reported in source
C26 tumor-bearing mice with or without OXFU chemotherapy
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
Selectively targeting cardiolipin with SS-31 partially counteracted body wasting
1 context sentence(design, population, supporting numbers)
Summary · context
The present study aimed at evaluating the ability of the mitochondria-targeted compound SS-31 to counteract muscle wasting and altered metabolism in C26-bearing (C26) mice either receiving chemotherapy (OXFU: oxaliplatin plus 5-fluorouracil) or not.
Show in the study text Report a problemFND-3367049701
02AnimalAnimal study (in vivo)Efficacy outcome
In C26 tumor-bearing mice, SS‑31 prevented the reduction of glycolytic myofiber area.
In plain wordsIn mice with cancer cachexia, SS‑31 prevented the shrinking of fast muscle fibres.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseGlycolytic myofiber area
Study
mousen: not reported in source
C26 tumor-bearing mice with or without OXFU chemotherapy
Outcome group
Muscle injury and repair · Musculoskeletal
Studied dose
Dose not stated
Source sentences
Summary
prevented the reduction of glycolytic myofiber area.
1 context sentence(design, population, supporting numbers)
Summary · context
The present study aimed at evaluating the ability of the mitochondria-targeted compound SS-31 to counteract muscle wasting and altered metabolism in C26-bearing (C26) mice either receiving chemotherapy (OXFU: oxaliplatin plus 5-fluorouracil) or not.
Show in the study text Report a problemFND-3367049702
03AnimalAnimal study (in vivo)Mechanism
In C26 tumor-bearing mice, SS‑31 increased muscle mitochondrial succinate dehydrogenase activity.
In plain wordsIn mice with cancer cachexia, SS‑31 raised the activity of a muscle mitochondrial enzyme (SDH).
Peptide
Elamipretide (SS-31)
Outcome
IncreaseMuscle mitochondrial SDH activity
Study
mousen: not reported in source
C26 tumor-bearing mice with or without OXFU chemotherapy
Outcome group
Mitochondrial function · Musculoskeletal
Studied dose
Dose not stated
Source sentences
Summary
SS-31 prompted muscle mitochondrial succinate dehydrogenase (SDH) activity
1 context sentence(design, population, supporting numbers)
Summary · context
The present study aimed at evaluating the ability of the mitochondria-targeted compound SS-31 to counteract muscle wasting and altered metabolism in C26-bearing (C26) mice either receiving chemotherapy (OXFU: oxaliplatin plus 5-fluorouracil) or not.
Show in the study text Report a problemFND-3367049703
04AnimalAnimal study (in vivo)Mechanism
In C26 tumor-bearing mice, SS‑31 rescued intracellular ATP levels.
In plain wordsIn mice with cancer cachexia, SS‑31 restored cell energy (ATP) levels.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseIntracellular ATP levels in muscle
Study
mousen: not reported in source
C26 tumor-bearing mice with or without OXFU chemotherapy
Outcome group
Mitochondrial function · Musculoskeletal
Studied dose
Dose not stated
Source sentences
Summary
rescued intracellular ATP levels, although it was unable to counteract mitochondrial protein loss.
1 context sentence(design, population, supporting numbers)
Summary · context
The present study aimed at evaluating the ability of the mitochondria-targeted compound SS-31 to counteract muscle wasting and altered metabolism in C26-bearing (C26) mice either receiving chemotherapy (OXFU: oxaliplatin plus 5-fluorouracil) or not.
Show in the study text Report a problemFND-3367049704
05AnimalAnimal study (in vivo)Mechanism
In C26 tumor-bearing mice, SS‑31 was unable to counteract mitochondrial protein loss.
In plain wordsIn mice with cancer cachexia, SS‑31 did not stop the loss of mitochondrial proteins.
Peptide
Elamipretide (SS-31)
Outcome
No significant changeMitochondrial protein loss
Study
mousen: not reported in source
C26 tumor-bearing mice with or without OXFU chemotherapy
Outcome group
Mitochondrial function · Musculoskeletal
Studied dose
Dose not stated
Source sentences
Summary
although it was unable to counteract mitochondrial protein loss.
1 context sentence(design, population, supporting numbers)
Summary · context
The present study aimed at evaluating the ability of the mitochondria-targeted compound SS-31 to counteract muscle wasting and altered metabolism in C26-bearing (C26) mice either receiving chemotherapy (OXFU: oxaliplatin plus 5-fluorouracil) or not.
Show in the study text Report a problemFND-3367049705
06AnimalAnimal study (in vivo)Efficacy outcome
In C26 mice receiving OXFU chemotherapy, progressively increased SS‑31 dosing had transient beneficial effects on body and muscle weight loss for 21 days, before a refractory end-stage condition at 28 days.
In plain wordsIn mice with cancer and chemotherapy, rising SS‑31 doses reduced body and muscle loss for 21 days, before an end-stage condition began.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseBody and muscle weight loss in C26 OXFU mice (up to 21 days)
Study
mousen: not reported in source
C26 tumor-bearing mice with or without OXFU chemotherapy
Outcome group
Body weight · Metabolic and weight
Studied dose
progressively increased dosing · 21 daysAs given in this study (mouse).
Source sentences
Summary
Progressively increased dosing of SS-31 to C26 OXFU mice showed transient (21 days) beneficial effects on body and muscle weight loss before the onset of a refractory end-stage condition (28 days).
1 context sentence(design, population, supporting numbers)
Summary · context
The present study aimed at evaluating the ability of the mitochondria-targeted compound SS-31 to counteract muscle wasting and altered metabolism in C26-bearing (C26) mice either receiving chemotherapy (OXFU: oxaliplatin plus 5-fluorouracil) or not.
Show in the study text Report a problemFND-3367049706
07AnimalAnimal study (in vivo)Mechanism
In C26 mice receiving OXFU chemotherapy, SS‑31 prevented mitochondrial loss at day 21.
In plain wordsIn mice with cancer and chemotherapy, SS‑31 prevented loss of mitochondria at day 21.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseMitochondrial loss at day 21 in C26 OXFU mice
Study
mousen: not reported in source
C26 tumor-bearing mice with or without OXFU chemotherapy
Outcome group
Mitochondrial function · Musculoskeletal
Studied dose
Dose not stated · 21 daysAs given in this study (mouse).
Source sentences
Summary
At day 21, SS-31 prevented mitochondrial loss
1 context sentence(design, population, supporting numbers)
Summary · context
The present study aimed at evaluating the ability of the mitochondria-targeted compound SS-31 to counteract muscle wasting and altered metabolism in C26-bearing (C26) mice either receiving chemotherapy (OXFU: oxaliplatin plus 5-fluorouracil) or not.
Show in the study text Report a problemFND-3367049707
08AnimalAnimal study (in vivo)Mechanism
In C26 mice receiving OXFU chemotherapy, SS‑31 prevented abnormal autophagy and mitophagy at day 21.
In plain wordsIn mice with cancer and chemotherapy, SS‑31 prevented abnormal cell recycling (autophagy) at day 21.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseAbnormal autophagy/mitophagy at day 21 in C26 OXFU mice
Study
mousen: not reported in source
C26 tumor-bearing mice with or without OXFU chemotherapy
Outcome group
Mitochondrial function · Musculoskeletal
Studied dose
Dose not stated · 21 daysAs given in this study (mouse).
Source sentences
Summary
abnormal autophagy/mitophagy.
1 context sentence(design, population, supporting numbers)
Summary · context
The present study aimed at evaluating the ability of the mitochondria-targeted compound SS-31 to counteract muscle wasting and altered metabolism in C26-bearing (C26) mice either receiving chemotherapy (OXFU: oxaliplatin plus 5-fluorouracil) or not.
Show in the study text Report a problemFND-3367049708
09AnimalAnimal study (in vivo)Mechanism
In C26 tumor-bearing mice, SS‑31 partially modulated the skeletal muscle and liver metabolome.
In plain wordsIn mice with cancer cachexia, SS‑31 partly changed the pattern of muscle and liver metabolites.
Peptide
Elamipretide (SS-31)
Outcome
Direction not reportedSkeletal muscle and liver metabolome
Study
mousen: not reported in source
C26 tumor-bearing mice with or without OXFU chemotherapy
Outcome group
Mitochondrial function · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
SS-31 partially modulated skeletal muscle and liver metabolome
1 context sentence(design, population, supporting numbers)
Summary · context
The present study aimed at evaluating the ability of the mitochondria-targeted compound SS-31 to counteract muscle wasting and altered metabolism in C26-bearing (C26) mice either receiving chemotherapy (OXFU: oxaliplatin plus 5-fluorouracil) or not.
Show in the study text Report a problemFND-3367049709

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

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