Open AccessMT‐102 prevents tissue wasting and improves survival in a rat model of severe cancer cachexia
Author(s) -
Pötsch Mareike S.,
Ishida Junichi,
Palus Sandra,
Tschirner Anika,
Haehling Stephan,
Doehner Wolfram,
Anker Stefan D.,
Springer Jochen
Publication year - 2020
Publication title -
journal of cachexia, sarcopenia and muscle
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.803
H-Index - 66
eISSN - 2190-6009
pISSN - 2190-5991
DOI - 10.1002/jcsm.12537
Subject(s) - cachexia , wasting , anabolism , placebo , medicine , wasting syndrome , skeletal muscle , endocrinology , catabolism , weight loss , sarcopenia , adipose tissue , lean body mass , cancer , protein catabolism , body weight , obesity , chemistry , metabolism , pathology , biochemistry , alternative medicine , amino acid
Background Cachexia, a common manifestation of malignant cancer, is associated with wasting of skeletal muscle and fat tissue. In this study, we investigated the effects of a new first in class anabolic catabolic transforming agent on skeletal muscle in a rat model of cancer cachexia. Methods Young male Wistar Han rats were intraperitoneally inoculated with 10 8 Yoshida hepatoma AH‐130 cells and once daily treated with 0.3 mg kg −1 , 3 mg kg −1 MT‐102, or placebo by gavage. Results Three mg kg −1 d −1 MT‐102 not only prevented progressive loss of fat mass (−6 ± 2 g vs ‐12 ± 1 g; P < 0.001); lean mass (+1 ± 10 g vs. −37 ± 2 g; P < 0.001) and body weight (+1 ± 13 g vs. −60 ± 2 g; P < 0.001) were remained. Quality of life was also improved as indicated by a higher food intake 12.9 ± 3.1 g and 4.3 ± 0.5 g, 3 mg kg −1 d −1 MT‐102 vs. placebo, respectively, P < 0.001) and a higher spontaneous activity (52 369 ± 6521 counts/24 h and 29 509 ± 1775 counts/24 h, 3 mg·kg ‐1 d ‐1 MT‐102 vs. placebo, respectively, P < 0.01) on Day 11. Most importantly, survival was improved (HR = 0.29; 95% CI: 0.16–0.51, P < 0.001). The molecular mechanisms behind these effects involve reduction of overall protein degradation and activation of protein synthesis, assessed by measurement of proteasome and caspase‐6 activity or Western blot analysis, respectively. Conclusions The present study shows that 3 mg kg −1 MT‐102 reduces catabolism, while inducing anabolism in skeletal muscle leading to an improved survival.