Suberoylanilide hydroxamic acid represses glioma stem-like cells
Posted on 2016-11-18 - 05:00
Abstract Background Glioma stem-like cells (GSCs) are proposed to be responsible for high resistance in glioblastoma multiforme (GBM) treatment. In order to find new strategies aimed at reducing GSC stemness and improving GBM patient survival, we investigated the effects and mechanism of a histone deacetylases (HDACs) inhibitor, suberoylanilide hydroxamic acid (SAHA), since HDAC activity has been linked to cancer stem-like cell (CSC) abundance and properties. Methods Human GBM cell lines were plated in serum-free suspension cultures allowed for sphere forming and CSC enrichment. Subsequently, upon SAHA treatment, the stemness markers, cell proliferation, and viability of GSCs as well as cellular apoptosis and senescence were examined in order to clarify whether inhibition of GSCs occurs. Results We demonstrated that SAHA attenuated cell proliferation and diminished the expression stemness-related markers (CD133 and Bmi1) in GSCs. Furthermore, at high concentrations (more than 5 μM), SAHA triggered apoptosis of GSCs accompanied by increases in both activation of caspase 8- and caspase 9-mediated pathways. Interestingly, we found that a lower dose of SAHA (1 μM and 2.5 μM) inhibited GSCs via cell cycle arrest and induced premature senescence through p53 up-regulation and p38 activation. Conclusion SAHA induces apoptosis and functions as a potent modulator of senescence via the p38-p53 pathway in GSCs. Our results provide a perspective on targeting GSCs via SAHA treatment, and suggest that SAHA could be used as a potent agent to overcome drug resistance in GBM patients.
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Hsu, Che-Chia; Chang, Wen-Chang; Hsu, Tsung-I; Liu, Jr-Jiun; Yeh, Shiu-Hwa; Wang, Jia-Yi; et al. (2016). Suberoylanilide hydroxamic acid represses glioma stem-like cells. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.3596465.v1
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AUTHORS (10)
CH
Che-Chia Hsu
WC
Wen-Chang Chang
TH
Tsung-I Hsu
JL
Jr-Jiun Liu
SY
Shiu-Hwa Yeh
JW
Jia-Yi Wang
JL
Jing-Ping Liou
CK
Chiung-Yuan Ko
KC
Kwang-Yu Chang
JC
Jian-Ying Chuang