title: Bortezomib inhibits C2C12 growth by inducing cell cycle arrest and apoptosis.
abstract: 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.
authors: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Soochow University, 199 Ren Ai Road, Suzhou 215123, China.
authors: S S
authors: SS
authors: Xing
authors: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Soochow University, 199 Ren Ai Road, Suzhou 215123, China.
authors: C C
authors: CC
authors: Shen
authors: Department of Nutrition and Kinesiology, University of Central Missouri, Warrensburg, MO 64093, USA.
authors: M P
authors: MP
authors: Godard
authors: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Soochow University, 199 Ren Ai Road, Suzhou 215123, China.
authors: J J
authors: JJ
authors: Wang
authors: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Soochow University, 199 Ren Ai Road, Suzhou 215123, China.
authors: Y Y
authors: YY
authors: Yue
authors: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Soochow University, 199 Ren Ai Road, Suzhou 215123, China.
authors: S T
authors: ST
authors: Yang
authors: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Soochow University, 199 Ren Ai Road, Suzhou 215123, China.
authors: Q
authors: Q
authors: Zhao
authors: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Soochow University, 199 Ren Ai Road, Suzhou 215123, China.
authors: S B
authors: SB
authors: Zhang
authors: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Soochow University, 199 Ren Ai Road, Suzhou 215123, China.
authors: T X
authors: TX
authors: Wang
authors: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Soochow University, 199 Ren Ai Road, Suzhou 215123, China.
authors: X L
authors: XL
authors: Yang
authors: Tulane University Heart and Vascular Institute, Tulane University School of Medicine, New Orleans, LA 70112, USA.
authors: P
authors: P
authors: Delafontaine
authors: Thrombosis and Hemostasis Key Lab, Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China. Electronic address: yaohua_song1@yahoo.com.
authors: Y
authors: Y
authors: He
authors: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Soochow University, 199 Ren Ai Road, Suzhou 215123, China. Electronic address: heyang1963@163.com.
authors: Y H
authors: YH
authors: Song
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000494:pharmacology*; D011719:Pyrazines / Q000494:pharmacology*
chemical_list: D001897:Boronic Acids; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Bortezomib; C2C12; Differentiation