ReferenceID 2021
Alantolactone ameliorates cancer cachexia-associated muscle atrophy mainly by inhibiting the STAT3 signaling pathway
Phytomedicine
BACKGROUND: Cancer cachexia is a serious metabolic disorder syndrome that is responsible for the deaths of approximately 30% of patients with cancer, but effective drugs for cancer cachexia are still lacking. Inflammator
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- Reference Id
- 2021
- Evidence Id
- 18611
- Core Evidence Id
- 18611
- Source Reference Id
- 4051
- Herb2 Reference Id
- HBREF004848
- Subject Paper Key
- HBIN028928_34861585
- Pubmed Id
- 34861585
- Doi
- 10.1016/j.phymed.2021.153858
- Paper Title
- Alantolactone ameliorates cancer cachexia-associated muscle atrophy mainly by inhibiting the STAT3 signaling pathway
- Paper Abstract
- BACKGROUND: Cancer cachexia is a serious metabolic disorder syndrome that is responsible for the deaths of approximately 30% of patients with cancer, but effective drugs for cancer cachexia are still lacking. Inflammatory cytokines such as TNF-alpha or IL-6 are involved in the induction of skeletal muscle atrophy and fat depletion in patients with cancer cachexia. PURPOSE: In this study, we assessed the therapeutic effects of the natural compound alantolactone (AL) on cancer cachexia and tried to clarify the mechanisms by which it ameliorates muscle atrophy. METHODS: The C26 tumor-bearing cancer cachexia mouse model was used to evaluate the efficacy of AL in alleviating cancer cachexia in vivo. The levels of IL-6 or TNF-alpha in mouse serum were detected using ELISA kits. Cultured C2C12 myotubes and 3T3-L1 adipocytes treated with conditioned medium of C26 tumor cells, IL-6 or TNF-alpha were employed as in vitro cancer cachexia models to examine the effects of AL in vitro. RESULTS: AL (5 or 10 mg/kg, qd, i.p.) protected mice with C26 tumors and cachexia from a loss of body weight and muscle wasting but only slightly ameliorated fat loss. The circulating level of IL-6 but not TNF-alpha was significantly decreased by AL. AL treatment significantly inhibited STAT3 activation in the gastrocnemius (GAS) muscle of cancer cachexia mice. AL (0.125, 0.25, 0.5 and 1 microM) dose-dependently ameliorated myotube atrophy and STAT3 activation in cultured C2C12 myotubes induced by conditioned medium from C26 tumor cells. AL also ameliorated C2C12 myotube atrophy induced by IL-6 and inhibited IL-6-mediated STAT3 activation. AL exhibited weak effects on ameliorating TNF-alpha-mediated myotube atrophy and NF-kappaB activation. Only AL at high doses of more than 5 microM ameliorated lipolysis and STAT3 activation induced in mature 3T3-L1 adipocytes by conditioned medium from C26 tumor cells. CONCLUSIONS: AL significantly ameliorated muscle atrophy in a cancer cachexia model mainly through the inhibition of the STAT3 pathway. AL might be a promising lead compound in the development of drug candidates for cancer cachexia therapy.
- Journal
- Phytomedicine
- Publish Year
- 2022
- Experiment Subject
- mouse; patient; 3t3-l1 adipocytes; c26 tumor cells; cultured c2c12 myotubes; mature 3t3-l1 adipocytes
- Experiment Type
- Animal Experiment
- Phenotype Related
- Muscle Wasting; C26 Tumor-bearing Cancer Cachexia; Tumor; Cachexia; Metabolic Disorder Syndrome; Skeletal Muscle Atrophy; Cancer; Muscle Atrophy; Cancer Cachexia; C26 Tumors
- Paper Title Cn
- Paper Title En
- Alantolactone ameliorates cancer cachexia-associated muscle atrophy mainly by inhibiting the STAT3 signaling pathway
- Bilingual Status
- semi_complete