Abstract
Cancer cachexia is a life‑threatening syndrome associated with myofiber damage. Tumor factors impair muscle regeneration by promoting myoblast apoptosis. Ghrelin is a multifunctional hormone with an anti‑apoptotic effect, but its mechanism of action is not fully understood. In the present study, we investigated whether the coculturing of C2C12 myoblasts with CT26 colon carcinoma cells may induce myoblast apoptosis, and whether acylated ghrelin (AG) and unacylated ghrelin (UnAG) may exert anti‑apoptotic effects. We found that the coculture induced myoblast apoptosis and increased tumor necrosis factor (TNF)‑α concentrations in the culture medium. Moreover, the coculture increased c‑Jun N‑terminal kinase (JNK) activity, suppressed Akt activity, increased the mitochondrial Bax/Bcl‑2 ratio, impaired mitochondrial membrane potential (Δψm), increased the cytosolic cytochrome c levels, and activated the caspase‑3/poly (ADP‑ribose) polymerase (PARP) cascade in myoblasts. We also found that either AG or UnAG inhibited these changes. The present study describes a novel in vitro model that can be employed to investigate cancer‑induced myoblast apoptosis, and our findings suggest a possible use for AG and UnAG in treating cancer cachexia.