Midazolam induces apoptosis in MA-10 mouse leydig tumor cells through caspase activation and the involvement of MAPK signaling pathway

Edmund Cheung So, Yu Xuan Lin, Chi Hao Tseng, Bo Syong Pan, Ka Shun Cheng, Kar Lok Wong, Lyh Jyh Hao, Yang Kao Wang, Bu Miin Huang

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Purpose: The present study aims to investigate how midazolam, a sedative drug for clinical use with cytotoxicity on neuronal and peripheral tissues, induced apoptosis in MA-10 mouse Leydig tumor cells. Methods: The apoptotic effect and underlying mechanism of midazolam to MA-10 cells were investigated by flow cytometry assay and Western blotting methods. Results: Data showed that midazolam induced the accumulation of the MA-10 cell population in the sub-G1 phase and a reduction in the G2/M phase in a time- and dose-dependent manner, suggesting an apoptotic phenomenon. Midazolam could also induce the activation of caspase-8, -9, and -3 and poly (ADP-ribose) polymerase proteins. There were no changes in the levels of Bax and cytochrome-c, whereas Bid was significantly decreased after midazolam treatment. Moreover, midazolam decreased both pAkt and Akt expression. In addition, midazolam stimulated the phosphorylation of p38 and c-Jun NH2-terminal kinase but not extracellular signal-regulated kinase. Conclusion: Midazolam could induce MA-10 cell apoptosis through the activation of caspase cascade, the inhibition of pAkt pathway, and the induction of p38 and c-Jun NH2-terminal kinase pathways.

Original languageEnglish
Pages (from-to)211-221
Number of pages11
JournalOncoTargets and Therapy
Volume7
DOIs
Publication statusPublished - Feb 13 2014

    Fingerprint

Keywords

  • Akt
  • Apoptosis
  • Caspase
  • MA-10 cell
  • MAPKs
  • Midazolam

ASJC Scopus subject areas

  • Oncology
  • Pharmacology (medical)

Cite this

So, E. C., Lin, Y. X., Tseng, C. H., Pan, B. S., Cheng, K. S., Wong, K. L., Hao, L. J., Wang, Y. K., & Huang, B. M. (2014). Midazolam induces apoptosis in MA-10 mouse leydig tumor cells through caspase activation and the involvement of MAPK signaling pathway. OncoTargets and Therapy, 7, 211-221. https://doi.org/10.2147/OTT.S56084