Journal article 731 views 109 downloads
Targeting Mitochondria by SS-31 Ameliorates the Whole Body Energy Status in Cancer- and Chemotherapy-Induced Cachexia
,
Paola Costelli,
Angela Corcelli,
Andrea Bonetto,
Hazel H Szeto,
Thomas M O'Connell,
Fabio Penna
Cancers, Volume: 13, Issue: 4
Swansea University Author:
Roberto Angelini
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DOI (Published version): 10.3390/cancers13040850
Abstract
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. : The present study aimed at evalu...
| Published in: | Cancers |
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| ISSN: | 2072-6694 |
| Published: |
2021
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa57169 |
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| Abstract: |
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. : 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. : 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. : 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. |
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| Item Description: |
Special Issue Cancer-Associated Cachexia |
| Keywords: |
SS-31, cancer cachexia, liver, metabolomics, mitochondria, muscle wasting |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
Università degli Studi di Torino Grant: Ex-60% funds V Foundation for Cancer Research Grant: V2017-021 American Cancer Society Grant: 132013-RSG-18-010-01-CCG Associazione Italiana per la Ricerca sul Cancro Grant: IG 2018-ID. 21963 project |
| Issue: |
4 |