1177974_Chitti,SV_2021.pdf (4.77 MB)
Repurposing of antibiotic sulfisoxazole inhibits lipolysis in pre-clinical model of cancer-associated cachexia
journal contribution
posted on 2021-09-06, 05:08 authored by Sai Vara Prasad ChittiSai Vara Prasad Chitti, Akbar Lulu MarzanAkbar Lulu Marzan, Sanjay ShahiSanjay Shahi, Taeyoung KangTaeyoung Kang, Pamali FonsekaPamali Fonseka, Suresh MathivananSuresh MathivananClinical management of cancer-associated cachexia, a multi-organ wasting syndrome, has been challenging without effective treatment strategies. An effective treatment that directly targets cancer-induced wasting is desperately needed to improve the quality of life and the survival of cancer patients. Recently, an antibiotic SFX was shown to have anti-tumour and anti-metastatic effects in mouse models of breast cancer. Hence, in this study, we examined the efficacy of SFX in the treatment of cancer-induced cachexia. C26 cachexic mice models were administered with SFX, and the tumour volume and body weight were regularly measured. Blood glucose, skeletal muscles, and adipose tissue were examined at the endpoint. Contrary to a previous study, SFX did not reduce the tumour volume in mice bearing C26 cells. Administration of SFX neither revealed any survival benefit nor rescued C26 cachectic mice from muscle wasting. Interestingly, SFX administration partially rescued (~10%) tumour-induced weight loss by preserving both the subcutaneous and intestinal fat mass. Together, these results suggest that the administration of SFX could partially rescue cancer-induced weight loss by inhibiting lipolysis. As anti-cachexia therapies are scarce, the results could facilitate the design of combinatorial therapies involving SFX, standard-of-care chemotherapeutics, and drugs that inhibit muscle atrophy for the treatment of cancer cachexia.
Funding
Suresh Mathivanan is supported by the Australian Research Council Future Fellowship (FT180100333), but the project was not funded by the basic science grant.
History
Publication Date
2021-07-22Journal
BiologyVolume
10Issue
8Article Number
700Pagination
11p.Publisher
MDPIISSN
2079-7737Rights Statement
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Publisher DOI
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