Skeletal muscle wasting is a hallmark of cancer cachexia. This metabolic syndrome is a major clinical problem in oncology and it is responsible for about 25% of cancer deaths. In particular, muscle loss in cachectic patients often leads to increased morbidity and mortality rates, decreased beneficial effects from chemotherapy treatment, and poor quality of life. For these reasons, the development of novel strategies to prevent muscle wasting during cancer cachexia is attracting increasing clinical interest. To date, no effective therapies for cachectic muscle are available. Recently, our research group reported that the small bromodomain inhibitor JQ1 enhances muscle fiber size and protects from dexamethasone-induced muscle atrophy in C2C12 myotubes, by counteracting skeletal muscle pro-atrophic pathways. Hence, in the present work we evaluated the effect of JQ1 treatment in skeletal muscle wasting during cancer cachexia. To this aim, C26 (adenocarcinoma cell line) bearing mice were chronically treated with JQ1 or vehicle. After 12 days, body weight, skeletal muscle weight and the anabolic/catabolic pathways involved in skeletal muscle homeostasis were analyzed. The results show that JQ1 treatment protects tumor-bearing mice from body weight loss and muscle wasting, suggesting that the epigenetic modulation mediated by bromodomain inhibitors may represent a promising therapeutic approach in the management of muscle wasting during cancer cachexia.
|Titolo:||Epigenetic therapy by JQ1 administration prevents skeletal muscle loss during cancer cachexia|
|Data di pubblicazione:||2014|
|Appare nelle tipologie:||1.5 Abstract in rivista|