Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25950483
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Identification of thioridazine, an antipsychotic drug, as an antiglioblastoma and
anticancer stem cell agent using public gene expression data
#MMPMID25950483
Cheng HW
; Liang YH
; Kuo YL
; Chuu CP
; Lin CY
; Lee MH
; Wu AT
; Yeh CT
; Chen EI
; Whang-Peng J
; Su CL
; Huang CY
Cell Death Dis
2015[May]; 6
(5
): e1753
PMID25950483
show ga
Glioblastoma (GBM) is a common and malignant tumor with a poor prognosis.
Glioblastoma stem cells (GSCs) have been reported to be involved in
tumorigenesis, tumor maintenance and therapeutic resistance. Thus, to discover
novel candidate therapeutic drugs for anti-GBM and anti-GSCs is an urgent need.
We hypothesized that if treatment with a drug could reverse, at least in part,
the gene expression signature of GBM and GSCs, this drug may have the potential
to inhibit pathways essential in the formation of GBM and thereby treat GBM.
Here, we collected 356 GBM gene signatures from public databases and queried the
Connectivity Map. We systematically evaluated the in vitro antitumor effects of
79 drugs in GBM cell lines. Of the drugs screened, thioridazine was selected for
further characterization because it has potent anti-GBM and anti-GSCs properties.
When investigating the mechanisms underlying the cytocidal effects of
thioridazine, we found that thioridazine induces autophagy in GBM cell lines, and
upregulates AMPK activity. Moreover, LC3-II was upregulated in U87MG sphere cells
treated with thioridazine. In addition, thioridazine suppressed GBM tumorigenesis
and induced autophagy in vivo. We not only repurposed the antipsychotic drug
thioridazine as a potent anti-GBM and anti-GSCs agent, but also provided a new
strategy to search for drugs with anticancer and anticancer stem cell properties.
free
free
free
