ArticleThe Biochemical journal2002
Torbafylline (HWA 448) inhibits enhanced skeletal muscle ubiquitin-proteasome-dependent proteolysis in cancer and septic rats.
Article in The Biochemical journal, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 71 citations in OpenAlex.
- Protein-energy wasting in chronic kidney disease: mechanisms responsible for loss of muscle mass and function.Kidney research and clinical practice · 2025Article
- Repurposing of Antibiotic Sulfisoxazole Inhibits Lipolysis in Pre-Clinical Model of Cancer-Associated Cachexia.Biology · 2021Article
- The impact of immobilisation and inflammation on the regulation of muscle mass and insulin resistance: different routes to similar end-points.The Journal of physiology · 2019Review
- A muscle-specific MuRF1-E2 network requires stabilization of MuRF1-E2 complexes by telethonin, a newly identified substrate.Journal of cachexia, sarcopenia and muscle · 2018Article
- UBE2B is implicated in myofibrillar protein loss in catabolic C2C12 myotubes.Journal of cachexia, sarcopenia and muscle · 2016Article
- Cardiac cachexia: hic et nunc.Journal of cachexia, sarcopenia and muscle · 2016Review
- Muscle wasting in disease: molecular mechanisms and promising therapies.Nature reviews. Drug discovery · 2015Review
- Role of E2-Ub-conjugating enzymes during skeletal muscle atrophy.Frontiers in physiology · 2015Review
- A view from above: cloud plots to visualize global metabolomic data.Analytical chemistry · 2013Article
- Role of IGF-I and the TNFα/NF-κB pathway in the induction of muscle atrogenes by acute inflammation.American journal of physiology. Endocrinology and metabolism · 2012Article
- Protein and Amino Acid Supplementation Does Not Alter Proteolytic Gene Expression following Immobilization.Journal of nutrition and metabolism · 2011Article
- Enhanced muscle shortening and impaired Ca2+ channel function in an acute septic myopathy model.Journal of neurology · 2010Article
- Cachexia in the non-obese diabetic mouse is associated with CD4+ T-cell lymphopenia.Immunology · 2008Article
- Pressure support ventilation attenuates ventilator-induced protein modifications in the diaphragm.Critical care (London, England) · 2008Article
- Roles and potential therapeutic targets of the ubiquitin proteasome system in muscle wasting.BMC biochemistry · 2007Review
- Glucocorticoids regulate mRNA levels for subunits of the 19 S regulatory complex of the 26 S proteasome in fast-twitch skeletal muscles.The Biochemical journal · 2004Article
- Ubiquitin-proteasome-dependent muscle proteolysis responds slowly to insulin release and refeeding in starved rats.The Journal of physiology · 2003Article
- Proteolysis in illness-associated skeletal muscle atrophy: from pathways to networks.Critical reviews in clinical laboratory sciencesReview
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of new pharmacological approaches for preventing muscle wasting in cancer is an important goal because cachectic patients display a reduced response to chemotherapy and radiotherapy. Xanthine derivatives such as pentoxifylline inhibit tumour necrosis factor-alpha (TNF) production, which has been implicated in the signalling of muscle wasting. However, the effect of pentoxifylline has been inconclusive in clinical trials. We report here the first direct evidence that daily injections of torbafylline (also known as HWA 448), another xanthine derivative, had no effect by itself on muscle proteolysis in control healthy rats. In cancer rats, the drug blocked the lipopolysaccharide-induced hyperproduction of TNF and prevented muscle wasting. In these animals HWA 448 suppressed the enhanced proteasome-dependent proteolysis, which is sensitive to the proteasome inhibitor MG132, and the accumulation of high-molecular-mass ubiquitin (Ub) conjugates in the myofibrillar fraction. The drug also normalized the enhanced muscle expression of Ub, which prevails in the atrophying muscles from cancer rats. In contrast, HWA 448 did not reduce the increased expression of either the 14 kDa Ub conjugating enzyme E2 or the ATPase and non-ATPase subunits of the 19 S regulatory complex of the 26 S proteasome, including the non-ATPase subunit S5a, which recognizes polyUb degradation signals. Finally, the drug also prevented muscle wasting in septic rats (which exhibit increased TNF production), and was much more potent than pentoxifylline or other xanthine derivatives. Taken together, the data indicate that HWA 448 is a powerful inhibitor of muscle wasting that blocks enhanced Ub-proteasome-dependent proteolysis in situations where TNF production rises, including cancer and sepsis.
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