Artemether suppresses cell proliferation and induces apoptosis in diffuse large B cell lymphoma cells

作者:Zhao, Xinying; Guo, Xudong; Yue, Wenqin; Wang, Jianmin; Yang, Jianmin*; Chen, Jie*
来源:Experimental and Therapeutic Medicine, 2017, 14(5): 4083-4090.
DOI:10.3892/etm.2017.5063

摘要

Artemether (ART), a derivative of the well-known anti-malaria drug artemisinin, demonstrates potent anti-cancer activity in various cancer cells, however its effects on lymphoma remain unknown. The present study demonstrated that ART significantly inhibited proliferation of diffuse large B cell lymphoma (DLBCL) in vivo and in vitro, and led to G0/G1 phase arrest. Mechanistic studies demonstrated that ART suppressed the expression of the cell cycle proteins cyclin dependent kinase (CDK) 2, 4, and Cyclin D1, and specifically repressed the proto-oncogene c-Myc, rather than regulating the extracellular signal-regulated kinase or protein kinase B signaling pathways (two key pathways involved in regulating cell proliferation). In addition, high-concentration ART treatment significantly induced the apoptosis of DLBCL cells by promoting the cleavage of Caspase-3 and Poly (ADP-ribose) polymerase (PARP) 1. Overall, the data indicated that ART exhibited anti-cancer activity by inhibiting the expression of cell cycle genes and c-Myc, and promoting Caspase-3 and PARP1 cleavage, which suggested that ART may serve as a dual pharmaceutical for the treatment DLBCL.