The main features of cancer cachexia include skeletal muscle atrophy, which can significantly reduce the quality of life of patients. Clinical treatment of cancer cachexia is mainly based on nutritional therapy and physical exercise; medication only improves appetite but does not reverse the symptoms of skeletal muscle wasting. In this work, we systematically studied the underlying molecular mechanisms by which cucurbitacin IIb (CuIIb) ameliorates muscle wasting in cancer cachexia both in vitro and in vivo. CuIIb significantly ameliorated the chief features of cancer cachexia in vivo, alleviating weight loss, food intake, muscle wasting, adipose tissue depletion, and organ weight reductions. In vitro, CuIIb (10 and 20 μM) dose-dependently attenuated conditioned medium (CM)-induced C2C12 myotube atrophy. Collectively, our findings demonstrated that CuIIb prevented the upregulation of the E3 ubiquitin ligase muscle atrophy Fbox protein (MAFbx), myosin heavy chain (MyHC), and myogenin (MyoG) and impacted protein synthesis and degradation. In addition, CuIIb decreased the phosphorylation of Tyr705 in STAT3 by regulating the IL-6/STAT3/FoxO pathway to reduce skeletal muscle atrophy in cancer cachexia.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/ptr.7811 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Body Composition in Cholangiocarcinoma Affects Immune Cell Populations in the Tumor and Normal Liver Parenchyma.
J Clin Exp Hepatol
November 2024
Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany.
Background: Due to malnutrition and tumor cachexia, body composition (BC) is frequently altered and known to adversely affect short- and long-term results in patients with cholangiocarcinoma (CCA). Here, we explored immune cell populations in the tumor and liver of CCA patients with respect to BC.
Methods: A cohort of 96 patients who underwent surgery for CCA was investigated by multiplexed immunofluorescence (MIF) techniques with computer-based analysis on whole-tissue slide scans to quantify and characterize immune cells in normal liver and tumor regions.
Novel oral compound Z526 mitigates cancer-associated cachexia via intervening NF-κB signaling and oxidative stress.
Genes Dis
March 2025
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
Cancer-associated cachexia (CAC) is a severe metabolic disorder syndrome mainly characterized by muscle and fat loss, which accounts for one-third of cancer-related deaths. No effective therapeutic approach that could fully reverse CAC is available. NF-κB signaling and oxidative stress play vital roles in both muscle atrophy and fat loss in CAC.
View Article and Find Full Text PDFPrognostic Value of the Modified Cachexia Index in Colorectal Cancer Patients Undergoing Curative Surgery.
Cancer Diagn Progn
January 2025
Department of Gastroenterological Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
Background/aim: The cachexia index (CXI) has been reported to be a useful indicator for predicting the prognosis of cancer patients. However, CXI calculation requires skeletal muscle index (SMI) measurements, which involves an analysis of computed tomography images using an imaging software program, which makes the calculation process highly complex and time-consuming. Recently, the modified cachexia index (mCXI), calculated using the urea-to-creatinine ratio (UCR) instead of SMI, has been reported to be a useful marker that is easier to calculate than CXI.
View Article and Find Full Text PDFSystemic metabolic crosstalk as driver of cancer cachexia.
Trends Endocrinol Metab
January 2025
Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center 'Guido Tarone', University of Torino, 10126 Torino, Italy. Electronic address:
Cachexia is a complex metabolic disorder characterized by negative energy balance due to increased consumption and lowered intake, leading to progressive tissue wasting and inefficient energy distribution. Once considered as passive bystander, metabolism is now acknowledged as a regulator of biological functions and disease progression. This shift in perspective mirrors the evolving understanding of cachexia itself, no longer viewed merely as a secondary consequence of cancer but as an active process.
View Article and Find Full Text PDFGhrelin-LEAP2 interactions along the stomach-liver axis.
Endocr J
December 2024
Forefront Research Center, Graduate School of Science, Osaka University, Osaka 560-0043, Japan.
Ghrelin produced in the stomach promotes food intake and GH secretion, and acts as an anabolic peptide during starvation. Ghrelin binds to the growth hormone secretagogue receptor, a G protein-coupled receptor (GPCR), whose high-resolution complex structures have been determined in the apo state and when bound to an antagonist. Anamorelin, a low-molecular-weight ghrelin agonist, has been launched in Japan for the treatment of cancer cachexia, and its therapeutic potential has attracted attention due to the various biological activities of ghrelin.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!