Tumor growth and chemotherapy alter skeletal muscle, cardiac, and hepatic amino acid pools in mice

Amino acids (AAs) play structural and metabolic roles in muscle, heart, and liver-tissues impacted by cancer and chemotherapy. Changes in AA profiles within these tissues have not been evaluated in response to tumor growth and chemotherapy. This study investigated how tumor growth with or without doxorubicin altered tissue-level amino acids. Female C57bl/6 mice (<i>n</i> = 7-10/group) were randomly assigned to groups: control, doxorubicin control at 3 and 7 days, 21-day tumor, 24-day tumor, 28-day tumor, 24-day tumor + doxorubicin, 28-day tumor + doxorubicin. Tumor groups were injected with E0771 cells in the right flank on <i>day 0</i>. Doxorubicin was administered once (intraperitoneally) at 10 mg/kg in doxorubicin control and tumor + doxorubicin groups on <i>day 21</i>, with endpoints at <i>day 24</i> and <i>28</i>. Muscle glutamate and aspartate were significantly depleted by <i>day 28</i> in both tumor and tumor + doxorubicin groups (<i>P</i> < 0.05), whereas proline, arginine, leucine, and isoleucine increased (<i>P</i> < 0.05). Hepatic aspartate was elevated by 21 days, and lysine by 24 days (<i>P</i> < 0.05). Cardiac glutamate was depleted at <i>days 21</i>, <i>24</i>, and <i>28</i> (<i>P</i> < 0.05). Notably, doxorubicin did not add to tumor-induced changes in muscle or heart. Tumor AAs remained largely stable. Tumor growth induced profound changes to skeletal muscle AA pools, reflecting impaired handling of AAs that could serve structural roles, or expand the substrate pool for ATP synthesis. Despite this, most tumor AAs remained stable over tumor growth. These results suggest a link between muscle wasting and skeletal muscle-derived AAs for tumor growth. Further work is needed to characterize the mechanisms mediating the observed changes in AA profiles.<b>NEW & NOTEWORTHY</b> This study demonstrates significantly perturbed amino acid pools within muscle as a result of tumor growth, with marginal additive effects of doxorubicin administration. Notably, tumor amino acid pools remain primarily unchanged despite muscle suggesting significant changes, which may be indicative of structural damage or reduced ability to produce energy.