Amelioration of muscle wasting by gintonin in cancer cachexia.
Neoplasia
; 23(12): 1307-1317, 2021 12.
Article
en En
| MEDLINE
| ID: mdl-34798386
ABSTRACT
Cancer cachexia is characterized by systemic inflammation, protein degradation, and loss of skeletal muscle. Despite extensive efforts to develop therapeutics, only few effective treatments are available to protect against cancer cachexia. Here, we found that gintonin (GT), a ginseng-derived lysophosphatidic acid receptor (LPAR) ligand, protected C2C12 myotubes from tumor necrosis factor α (TNFα)/interferon γ (IFNγ)- induced muscle wasting condition. The activity of GT was found to be dependent on LPAR/Gαi2, as the LPAR antagonist Ki16425 and Gαi2 siRNA abolished the anti-atrophic effects of GT on myotubes. GT suppressed TNFα-induced oxidative stress by reducing reactive oxygen species and suppressing inflammation-related genes, such as interleukin 6 (IL-6) and NADPH oxidase 2 (NOX-2). In addition, GT exhibited anti-atrophy effects in primary normal human skeletal myoblasts. Further, GT protected against Lewis lung carcinoma cell line (LLC1)-induced cancer cachexia in a mouse model. Specifically, GT rescued the lower levels of grip strength, hanging, and cross-sectional area caused by LLC1. Collectively, our findings suggest that GT may be a good therapeutic candidate for protecting against cancer cachexia.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Caquexia
/
Extractos Vegetales
/
Músculo Esquelético
/
Neoplasias
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Neoplasia
Asunto de la revista:
NEOPLASIAS
Año:
2021
Tipo del documento:
Article