dc.contributor.author
Yuan, Luping
dc.contributor.author
Springer, Jochen
dc.contributor.author
Palus, Sandra
dc.contributor.author
Busquets, Silvia
dc.contributor.author
Jové, Queralt
dc.contributor.author
Alves de Lima Junior, Edson
dc.contributor.author
Anker, Markus S.
dc.contributor.author
von Haehling, Stephan
dc.contributor.author
Álvarez Ladrón, Natalia
dc.contributor.author
Millman, Oliver
dc.contributor.author
Oosterlee, Annemijn
dc.contributor.author
Szymczyk, Agata
dc.contributor.author
López‐Soriano, Francisco Javier
dc.contributor.author
Anker, Stefan D.
dc.contributor.author
Coats, Andrew J.S.
dc.contributor.author
Argiles, Josep M.
dc.date.accessioned
2024-12-20T12:54:57Z
dc.date.available
2024-12-20T12:54:57Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/46063
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-45772
dc.description.abstract
Background: Beta-blockers and selected stereoisomers of beta-blockers, like bisoprolol and S-pindolol (ACM-001), have been shown to be effective in preclinical cancer cachexia models. Here, we tested the efficacy of stereoisomers of oxprenolol in two preclinical models of cancer cachexia-the Yoshida AH-130 rat model and the Lewis lung carcinoma (LLC) mouse model.
Methods and Results: In the Yoshida AH130 hepatoma rat cancer cachexia model and compared with placebo, 50 mg/kg/d S-oxprenolol (HR: 0.49, 95% CI: 0.28-0.85, P = 0.012) was superior to 50 mg/kg/d R-oxprenolol (HR: 0.83, 95% CI 0.38-1.45, P = 0.51) in reducing mortality (= reaching ethical endpoints). Combination of the three doses (12.5, 25 and 50 mg/kg/d) that had a significant effect on body weight loss in the S-oxprenolol groups vs the same combination of the R-oxprenolol groups lead to a significantly improved survival of S-oxprenolol vs R-oxprenolol (HR: 1.61, 95% CI: 1.08-2.39, P = 0.0185). Interestingly, there is a clear dose dependency in S-oxprenolol-treated (5, 12.5, 25 and 50 mg/kg/d) groups, which was not observed in groups treated with R-oxprenolol. A dose-dependent attenuation of weight and lean mass loss by S-oxprenolol was seen in the Yoshida rat model, whereas R-oxprenolol had only had a significant effect on fat mass. S-oxprenolol also non-significantly reduced weight loss in the LLC model and also improved muscle function (grip strength 428 +/- 25 and 539 +/- 37 g/100 g body weight for placebo and S-oxprenolol, respectively). However, there was only a minor effect on quality of life indicators food intake and spontaneous activity in the Yoshida model (25 mg/kg/S-oxprenolol: 11.9 +/- 2.5 g vs placebo: 4.9 +/- 0.8 g, P = 0.013 and also vs 25 mg/kg/d R-oxprenolol: 7.5 +/- 2.6 g, P = 0.025). Both enantiomers had no effects on cardiac dimensions and function at the doses used in this study. Western blotting of proteins involved in the anabolic/catabolic homoeostasis suggest that anabolic signalling is persevered (IGF-1 receptor, Akt) and catabolic signalling is inhibited (FXBO-10, TRAF-6) by S-pindolol, but not he R-enantiomer. Expression of glucose transporters Glut1 and Glut 4 was similar in all groups, as was AMPK.
Conclusions: S-oxprenolol is superior to R-oxprenolol in cancer cachexia animal models and shows promise for a human application in cancer cachexia.
en
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject
Cancer cachexia
en
dc.subject
S-oxprenolol
en
dc.subject
Intervention
en
dc.subject
Beta-blocker
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
The atypical β‐blocker S‐oxprenolol reduces cachexia and improves survival in a rat cancer cachexia model
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1002/jcsm.13116
dcterms.bibliographicCitation.journaltitle
Journal of Cachexia, Sarcopenia and Muscle
dcterms.bibliographicCitation.number
1
dcterms.bibliographicCitation.originalpublishername
Wiley
dcterms.bibliographicCitation.pagestart
653
dcterms.bibliographicCitation.pageend
660
dcterms.bibliographicCitation.volume
14
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.funding
DEAL Wiley
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
36346141
dcterms.isPartOf.issn
2190-5991
dcterms.isPartOf.eissn
2190-6009