Response of male and female mice to chronic alcohol use before and during cancer.

With its carcinogenic properties and ability to adversely affect skeletal muscle, alcohol intake before and during the development of cancer may exacerbate skeletal muscle complications like cancer cachexia. Any sex-specific effects of alcohol consumption before and during cancer also remain undefined. Presently, male and female mice were treated with a control alcohol-free liquid diet (CON) or a 20% ethanol (kcal/day) liquid diet (EtOH) for 7 weeks. Cancer groups (either CON or ETOH), were then inoculated with C26 colon cancer cells and gastrocnemius muscles were collected ∼ 2 weeks later. Alcohol decreased bodyweight and adipose tissue weight at euthanasia in male cancer mice, but this alcohol effect was absent in females. Cancer-induced muscle atrophy was evident in the soleus, plantaris, gastrocnemius and quadriceps muscle of both male and female mice, with alcohol only augmenting these effects in the gastrocnemius of male mice. In the gastrocnemius, AMPK T172 phosphorylation (Thr172) and REDD1 content was higher with cancer in males, while in females, alcohol and cancer increased AMPK T172 and alcohol alone augmented REDD1 content. Peptide chain elongation was likely impaired by alcohol and cancer only in males as eEF2 Thr56 was elevated. Cancer, but not alcohol, led to lower phosphorylation of proteins in the mTORC1 pathway in female, but not male muscle. Protein ubiquitination was higher in alcohol-treated females but not males. Overall, male and female mice displayed divergent responses relative to their same sex controls in response to alcohol consumption before and during cancer.