β‑carotene attenuates muscle wasting in cancer cachexia by regulating myogenesis and muscle atrophy

Cancer cachexia is a metabolic disease involving multiple organs, which is accompanied by the depletion of muscle tissue and is associated with ~20% of cancer-related deaths. Muscle wasting is a critical factor in cancer cachexia. β-carotene (BC) has been shown to increase muscle mass and hypertrophy in healthy mice. However, its effects on muscle tissue dysregulation in cancer cachexia have yet to be studied. In the present study, 5-week-old male C57BL/6J mice were injected with 1×10(6) Lewis lung carcinoma (LLC) cells to induce cancer cachexia; then the mice were administered BC (4 or 8 mg/kg) for 22 days to assess its effects on muscle atrophy in the gastrocnemius muscles. The effects of BC on inflammatory cytokines, myogenesis and muscle atrophy were evaluated using C2C12 myotubes treated with LLC-conditioned media. BC supplementation significantly suppressed tumor growth, inflammatory cytokines, and hepatic gluconeogenesis in the LLC-induced cancer cachexia mouse model, while also improving muscle weight and grip strength. These effects are considered to be mediated by the PI3K/Akt pathway and through regulation of muscle atrophy. Moreover, BC treatment was associated with the recovery of LLC-conditioned media-induced muscle differentiation deficits and muscle atrophy in C2C12 myotubes. These findings indicate BC as a potential novel therapeutic agent for cancer cachexia.