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| Status |
Public on Dec 31, 2015 |
| Title |
Curcumin Effectively Depletes Hepatic Cancer Stem-Like Cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
Five human hepatoma cell lines with and without curcumin
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| Contributor(s) |
Marquardt JU |
| Citation(s) |
25937435 |
| Submission date |
Jul 23, 2014 |
| Last update date |
Aug 13, 2018 |
| Contact name |
Jens U. Marquardt |
| E-mail(s) |
marquarj@uni-mainz.de
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| Phone |
496131176775
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| Organization name |
University of Mainz
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| Department |
Department of Medicine I
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| Street address |
Langenbeckstrasse 1
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| City |
Mainz |
| State/province |
-- |
| ZIP/Postal code |
55131 |
| Country |
Germany |
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| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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| Samples (30)
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| Relations |
| BioProject |
PRJNA256008 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE59713_RAW.tar |
26.2 Mb |
(http)(custom) |
TAR |
| GSE59713_non-normalized.txt.gz |
8.8 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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