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

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

来源：OncoTargets and Therapy, 2014, 7: 211-221.

DOI：10.2147/OTT.S56084

• midazolam
• apoptosis
• MA-10 cell
• caspase
• Akt
• MAPKs

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. %26lt;br%26gt;Methods: The apoptotic effect and underlying mechanism of midazolam to MA-10 cells were investigated by flow cytometry assay and Western blotting methods. %26lt;br%26gt;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. %26lt;br%26gt;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.

• 出版日期2014
• 单位中国医科大学