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Title: Curcumin Effectively Depletes Hepatic Cancer Stem-Like Cells      
dateReleased:
12-31-2015
description:
The cancer stem cells (CSCs) have important therapeutic implications for multi-resistant cancers including hepatocellular carcinoma (HCC). Among the key pathways frequently activated in liver CSCs is NF-kB signaling. Here we evaluated the CSCs-depleting potential of NF-kB inhibition in liver cancer achieved by IKK inhibitor curcumin and specific peptide SN50 . The effects on CSCs were assessed by analysis of Side Population (SP) and expression levels of CSC-related genes as determined by RT-qPCR, gene expression microarray, EMSA, and Western blotting. Curcumin caused anti-proliferative and pro-apoptotic responses directly related to the extent of NF-kB inhibition. In curcumin-sensitive tumor cells, the treatment led to a selective CSC depletion as evidenced by a reduced SP size, decreased sphere formation, down-regulation of CSC markers and suppressed tumorigenicity. Similarly, NF-kB inhibition by SN50 caused a general suppression of cell growth accompanied by a reduced SP fraction. In contrast, curcumin-resistant cells exhibited a paradoxical increase in proliferation and expression of CSC markers. Mechanistically, CSC-depleting activity of curcumin was exerted by the NF-kB-mediated HDAC inhibition causing down-regulation of c-MYC and other key oncogenic targets. Co-administration of the class I/II HDAC inhibitor trichostatine sensitized resistant cells to curcumin. Further, integration of a predictive signature of curcumin sensitity with our HCC database indicated that HCC patients with poor prognosis and progenitor features are most likely to benefit from NF-kB inhibition. These results demonstrate that NF-kB inhibition can specifically target CSC populations and suggest a potential for combined inhibition of NF-kB and HDAC signaling for treatment of liver cancer patients with poor prognosis. Five human hepatoma cell lines with and without curcumin
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-59713
refinement:
raw
alternateIdentifiers:
59713
keywords:
functional genomics
dateModified:
01-11-2016
availability:
available
types:
gene expression
name:
Homo sapiens
ID:
A-GEOD-10558
name:
Illumina HumanHT-12 V4.0 expression beadchip
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-59713/E-GEOD-59713.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-59713/E-GEOD-59713.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE59713
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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