Reversine, a selective MPS1 inhibitor, induced autophagic cell death via diminished glucose uptake and ATP production in cholangiocarcinoma cells

PeerJ

article

Piya Prajumwongs¹  Orawan Waenphimai¹  Kulthida Vaeteewoottacharn¹  Sopit Wongkham¹  Kanlayanee Sawanyawisuth¹ 

[1] Department of Biochemistry, Faculty of Medicine, Khon Kaen University;Cholangiocarcinoma Research Institute, Faculty of Medicine, Khon Kaen University

关键词: Reversine;    MPS1;    Cholangiocarcinoma;    Autophagy;    Apoptosis;    GLUT1;   

DOI  :  10.7717/peerj.10637

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

Reversine is a selective inhibitor of mitotic kinase monopolar spindle 1 (MPS1) and has been reported as an anticancer agent in various cancers. The effects of reversine on bile duct cancer, cholangiocarcinoma (CCA), a lethal cancer in Northeastern Thailand, were investigated. This study reports that reversine inhibited cell proliferation of CCA cell lines in dose- and time-dependent manners but had less inhibitory effect on an immortalized cholangiocyte cell line. Reversine also triggered apoptotic cell death by decreasing anti-apoptotic proteins, Bcl-XL and Mcl-1, increasing Bax pro-apoptotic protein and activating caspase-3 activity. Moreover, reversine induced autophagic cell death by increasing LC3-II and Beclin 1 while decreasing p62. Reversine activated autophagy via the AKT signaling pathway. Additionally, this study demonstrated for the first time that reversine could diminish the expression of Hypoxia-Inducible Factor 1- alpha (HIF-1α) and glucose transporter 1 (GLUT1), resulting in a reduction of glucose uptake and energy production in CCA cell lines. These findings suggest that reversine could be a good candidate as an alternative or supplementary drug for CCA treatment.

【 授权许可】

CC BY