(P13-011-23) Naringenin to Prevent Immobility and Loss of Muscle Function Caused by Cancer Cachexia in Mice

Objectives: Cancer cachexia, a progressive wasting of adipose and skeletal muscle, frequently occurs in cancer patients and is responsible for up to 20% of cancer related deaths. Many cancer therapies neglect treating reductions in physical activity and muscle function, which are associated with increased risk of death. Naringenin is a phytochemical found in citrus fruits that has anti-inflammatory and anticancer activities and may promote physical activity and preserve muscle function. This study will investigate whether naringenin can preserve or increase locomotor activity and muscle function in mice with cancer cachexia and determine the relationship between hypothalamic and serum IL-1β levels with locomotor activity and muscle function.

Methods: 24 male CD2F1 mice will be implanted with electronic telemetry transmitters prior to starting diets to continuously monitor locomotor activity. Mice will be fed a standardized diet supplemented with (NAR) or without (CON) 2% naringenin starting two weeks before being inoculated with 1x10⁶ C26 adenocarcinoma cells (+) or PBS (-). Final groups will be 8 (NAR+), 4 (NAR-), 8 (CON+), 4 (CON-). Mice will undergo muscle function tests to determine maximal contractile force of the gastroc and time to fatigue before and after C26 inoculation. IL-1β levels will be measured from hypothalamic tissue and serum using specific anti-mouse ELISAs.

Results: We expect tumor bearing mice fed naringenin to have significantly higher levels of locomotor activity and muscle function compared to tumor bearing mice fed a control diet at the onset of cancer cachexia. We further expect reductions in hypothalamic and serum IL-1β levels will be predictive of the preservation of locomotor activity and muscle function.

Conclusions: If successful, naringenin may be a promising adjuvant therapy that would warrant further investigation in future clinical trials involving patients with cancer cachexia.

Funding Sources: This project will be supported by the Center for Advanced Functional Foods Research and Enterprise.