Nilotinib impairs skeletal myogenesis by increasing myoblast proliferation.

Skeletal Muscle
Osvaldo ContrerasEnrique Brandan

Abstract

Tyrosine kinase inhibitors (TKIs) are effective therapies with demonstrated antineoplastic activity. Nilotinib is a second-generation FDA-approved TKI designed to overcome Imatinib resistance and intolerance in patients with chronic myelogenous leukemia (CML). Interestingly, TKIs have also been shown to be an efficient treatment for several non-malignant disorders such fibrotic diseases, including those affecting skeletal muscles. We investigated the role of Nilotinib on skeletal myogenesis using the well-established C2C12 myoblast cell line. We evaluated the impact of Nilotinib during the time course of skeletal myogenesis. We compared the effect of Nilotinib with the well-known p38 MAPK inhibitor SB203580. MEK1/2 UO126 and PI3K/AKT LY294002 inhibitors were used to identify the signaling pathways involved in Nilotinib-related effects on myoblast. Adult primary myoblasts were also used to corroborate the inhibition of myoblasts fusion and myotube-nuclei positioning by Nilotinib. We found that Nilotinib inhibited myogenic differentiation, reducing the number of myogenin-positive myoblasts and decreasing myogenin and MyoD expression. Furthermore, Nilotinib-mediated anti-myogenic effects impair myotube formation, myosin heavy chai...Continue Reading

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Citations

Jan 15, 2021·Comprehensive Reviews in Food Science and Food Safety·Kwang-Hwan ChoiChang-Kyu Lee
Mar 30, 2021·Frontiers in Cell and Developmental Biology·Fabián MontecinoHugo Olguín
Dec 24, 2020·Cancer Research·Thomas K SinYi-Ping Li
May 1, 2021·International Journal of Molecular Sciences·Seo-Mi-Gon Jeong, Tae-Jin Yoon

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Methods Mentioned

BETA
electrophoresis
PCR
X-ray
dissection

Software Mentioned

DiscoveRx KINOMEscan®
Image J
NIS
Prism
DiscoveRx
Elements AR
Pairwise Alignment
ImageJ
JSmol
[UNK] Compound Profile Visualization

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