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

Zachary C Ryan; Theodore A Craig; Xuewei Wang; Philippe Delmotte; Jeffrey L Salisbury; Ian R Lanza; Gary C Sieck; Rajiv Kumar

doi:10.1016/j.bbrc.2018.01.092

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

Biochem Biophys Res Commun. 2018 Feb 5;496(2):746-752. doi: 10.1016/j.bbrc.2018.01.092.

Authors

Zachary C Ryan¹, Theodore A Craig¹, Xuewei Wang², Philippe Delmotte³, Jeffrey L Salisbury⁴, Ian R Lanza⁵, Gary C Sieck³, Rajiv Kumar⁶

Affiliations

¹ Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA; Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
² Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
³ Department of Physiology and Biomedical Engineering, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
⁴ Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
⁵ Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA; Division of Endocrinology/Metabolism, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
⁶ Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA; Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA; Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA; Division of Endocrinology/Metabolism, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Electronic address: rkumar@mayo.edu.

Abstract

Cancer cachexia is associated with muscle weakness and atrophy. We investigated whether 1α,25-dihydroxyvitamin D₃ (1α,25(OH)₂D₃), 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. 1α,25(OH)₂D₃ reverses the tumor cell-mediated changes in mitochondrial oxygen consumption and proteasomal activity, without changing pyruvate dehydrogenase activity. 1α,25(OH)₂D₃ might be useful in treatment of weakness seen in association with CC.

Keywords: 1α,25-dihydroxyvitamin D(3); Cancer; Gene expression; Mitochondria; Oxygen consumption; Skeletal muscle.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Calcitriol / pharmacology*
Carcinoma, Lewis Lung / complications
Carcinoma, Lewis Lung / metabolism
Carcinoma, Lewis Lung / pathology
Cell Line
Cell Line, Tumor
Humans
Mitochondria / drug effects*
Mitochondria / metabolism
Mitochondria / pathology
Muscle Weakness / drug therapy*
Muscle Weakness / etiology*
Muscle Weakness / metabolism
Muscle Weakness / pathology
Myoblasts, Skeletal / drug effects*
Myoblasts, Skeletal / metabolism
Myoblasts, Skeletal / pathology
Neoplasms / complications*
Neoplasms / metabolism
Neoplasms / pathology
Oxygen Consumption / drug effects
Vitamins / pharmacology*

Substances

Vitamins
Calcitriol

Abstract

Publication types

MeSH terms

Substances

Grants and funding