Bortezomib inhibits C2C12 growth by inducing cell cycle arrest and apoptosis

•Bortezomib (BTZ) inhibits myogenin expression and myotube formation.•BTZ causes cell cycle arrest in C2C12 cells.•BTZ reduces C2C12 cell viability.•BTZ induced apoptosis in C2C12 cells.•The apoptosis induced by BTZ was associated with reduced expression of p-ERK. Proteosome inhibitors such as borte...

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Bibliographic Details
Published in:	Biochemical and biophysical research communications Vol. 445; no. 2; pp. 375 - 380
Main Authors:	Xing, S.S., Shen, C.C., Godard, M.P., Wang, J.J., Yue, Y.Y., Yang, S.T., Zhao, Q., Zhang, S.B., Wang, T.X., Yang, X.L., Delafontaine, P., He, Y., Song, Y.H.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 07-03-2014
Subjects:	Animals Apoptosis - drug effects Boronic Acids - pharmacology Bortezomib C2C12 Cell Line Cell Survival - drug effects Differentiation Down-Regulation - drug effects Extracellular Signal-Regulated MAP Kinases - genetics G2 Phase Cell Cycle Checkpoints - drug effects M Phase Cell Cycle Checkpoints - drug effects Mice Muscle Fibers, Skeletal - cytology Muscle Fibers, Skeletal - drug effects Muscle Fibers, Skeletal - metabolism Proteasome Inhibitors - pharmacology Pyrazines - pharmacology Differentiation C2C12 Bortezomib
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Summary:	•Bortezomib (BTZ) inhibits myogenin expression and myotube formation.•BTZ causes cell cycle arrest in C2C12 cells.•BTZ reduces C2C12 cell viability.•BTZ induced apoptosis in C2C12 cells.•The apoptosis induced by BTZ was associated with reduced expression of p-ERK. Proteosome inhibitors such as bortezomib (BTZ) have been used to treat muscle wasting in animal models. However, direct effect of BTZ on skeletal muscle cells has not been reported. In the present study, our data showed that C2C12 cells exhibited a dose-dependent decrease in cell viability in response to increasing concentrations of BTZ. Consistent with the results of cell viability, Annexin V/PI analysis showed a significant increase in apoptosis after exposing the cells to BTZ for 24h. The detection of cleaved caspase-3 further confirmed apoptosis. The apoptosis induced by BTZ was associated with reduced expression of p-ERK. Cell cycle analysis revealed that C2C12 cells underwent G2/M cell cycle arrest when incubated with BTZ for 24h. Furthermore, BTZ inhibited formation of multinucleated myotubes. The inhibition of myotube formation was accompanied by decreased expression of Myogenin. Our data suggest that BTZ induces cell death and inhibits differentiation of C2C12 cells at clinically relevant doses.
Bibliography:	These authors contributed equally to this work.
ISSN:	0006-291X 1090-2104
DOI:	10.1016/j.bbrc.2014.02.008