1α,25-dihydroxyvitamin D3 mitigates cancer cell mediated mitochondrial dysfunction in human skeletal muscle cells

Cancer cachexia is associated with muscle weakness and atrophy. We investigated whether 1 alpha,25-dihydroxyvitamin D-3 (1 alpha,25(OH)(2)D-3), which has previously been shown to increase skeletal myoblast oxygen consumption rate, could reverse the deleterious effects of tumor cell conditioned medium on myoblast function. Conditioned medium from Lewis lung carcinoma (LLC1) cells inhibits oxygen consumption, increases mitochondrial fragmentation, inhibits pyruvate dehydrogenase activity, and enhances proteasomal activity in human skeletal muscle myoblasts. 1 alpha,25(OH)(2)D-3 reverses the tumor cell mediated changes in mitochondrial oxygen consumption and proteasomal activity, without changing pyruvate dehydrogenase activity. 1 alpha,25(OH)(2)D-3 might be useful in treatment of weakness seen in association with CC. (C) 2018 The Author(s). Published by Elsevier Inc.