|
Publication
|
Title of Article |
Reversine, a selective MPS1 inhibitor, induced autophagic cell death via diminished glucose uptake and ATP production in cholangiocarcinoma cells |
Date of Acceptance |
2 December 2020 |
Journal |
Title of Journal |
PeerJ |
Standard |
ISI |
Institute of Journal |
PeerJ Inc. |
ISBN/ISSN |
|
Volume |
2021 |
Issue |
9 |
Month |
January |
Year of Publication |
2021 |
Page |
e10637 |
Abstract |
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-1) 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. |
Keyword |
Reversine, MPS1, Cholangiocarcinoma, Autophagy, Apoptosis, GLUT1 |
Author |
|
Reviewing Status |
มีผู้ประเมินอิสระ |
Status |
ตีพิมพ์แล้ว |
Level of Publication |
นานาชาติ |
citation |
true |
Part of thesis |
true |
Attach file |
|
Citation |
0
|
|
|
|
|
|
|