The NFκB inhibitor, SN50, induces differentiation of glioma stem cells and suppresses their oncogenic phenotype

Li Zhang; Xingcong Ren; Yan Cheng; Xiuping Liu; Joshua E. Allen; Yi Zhang; Yunsheng Yuan; Siu Yuan Huang; Weiwei Yang; Arthur Berg; Becky S. Webb; James Connor; Chang Gong Liu; Zhimin Lu; Wafik S. El-Deiry; Jin Ming Yang

doi:10.4161/cbt.28158

The NFκB inhibitor, SN50, induces differentiation of glioma stem cells and suppresses their oncogenic phenotype

Li Zhang, Xingcong Ren, Yan Cheng, Xiuping Liu, Joshua E. Allen, Yi Zhang, Yunsheng Yuan, Siu Yuan Huang, Weiwei Yang, Arthur Berg, Becky S. Webb, James Connor, Chang Gong Liu, Zhimin Lu, Wafik S. El-Deiry, Jin Ming Yang

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

The malignant phenotype of glioblastoma multiforme (GBM) is believed to be largely driven by glioma stem-like cells (GSCs), and targeting GSCs is now considered a promising new approach to treatment of this devastating disease. Here, we show that SN50, a cell-permeable peptide inhibitor of NFκB, induced robust differentiation of human GSCs, causing loss of their oncogenic potential. We observed that following treatment of GSCs with SN50, their differentiated progeny cells showed significant decreases in their capability to form neuro-spheres and to invade in vitro and a reduction in their tumorigenicity in mouse xenograft models, but had increased sensitivity to the chemotherapeutic drug temozolomide and to radiation treatment. These results suggest that blocking the NFκB pathway may be explored as a useful mean to induce differentiation of GSCs, and provide another supportive evidence for the promise of differentiation therapy in treatment of malignant brain tumors.

Original language	English (US)
Pages (from-to)	602-611
Number of pages	10
Journal	Cancer Biology and Therapy
Volume	15
Issue number	5
DOIs	https://doi.org/10.4161/cbt.28158
State	Published - May 2014

Keywords

Brain tumor
Differentiation
Glioma stem cells
NFκB inhibitor
SN50

ASJC Scopus subject areas

Molecular Medicine
Oncology
Pharmacology
Cancer Research

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Zhang, L., Ren, X., Cheng, Y., Liu, X., Allen, J. E., Zhang, Y., Yuan, Y., Huang, S. Y., Yang, W., Berg, A., Webb, B. S., Connor, J., Liu, C. G., Lu, Z., El-Deiry, W. S., & Yang, J. M. (2014). The NFκB inhibitor, SN50, induces differentiation of glioma stem cells and suppresses their oncogenic phenotype. Cancer Biology and Therapy, 15(5), 602-611. https://doi.org/10.4161/cbt.28158

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title = "The NFκB inhibitor, SN50, induces differentiation of glioma stem cells and suppresses their oncogenic phenotype",

abstract = "The malignant phenotype of glioblastoma multiforme (GBM) is believed to be largely driven by glioma stem-like cells (GSCs), and targeting GSCs is now considered a promising new approach to treatment of this devastating disease. Here, we show that SN50, a cell-permeable peptide inhibitor of NFκB, induced robust differentiation of human GSCs, causing loss of their oncogenic potential. We observed that following treatment of GSCs with SN50, their differentiated progeny cells showed significant decreases in their capability to form neuro-spheres and to invade in vitro and a reduction in their tumorigenicity in mouse xenograft models, but had increased sensitivity to the chemotherapeutic drug temozolomide and to radiation treatment. These results suggest that blocking the NFκB pathway may be explored as a useful mean to induce differentiation of GSCs, and provide another supportive evidence for the promise of differentiation therapy in treatment of malignant brain tumors.",

keywords = "Brain tumor, Differentiation, Glioma stem cells, NFκB inhibitor, SN50",

author = "Li Zhang and Xingcong Ren and Yan Cheng and Xiuping Liu and Allen, {Joshua E.} and Yi Zhang and Yunsheng Yuan and Huang, {Siu Yuan} and Weiwei Yang and Arthur Berg and Webb, {Becky S.} and James Connor and Liu, {Chang Gong} and Zhimin Lu and El-Deiry, {Wafik S.} and Yang, {Jin Ming}",

note = "Funding Information: Supported by grants from the US Public Health Service CA135038, the National Natural Sciences Foundation of China (81101913), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).",

year = "2014",

month = may,

doi = "10.4161/cbt.28158",

language = "English (US)",

volume = "15",

pages = "602--611",

journal = "Cancer Biology and Therapy",

issn = "1538-4047",

publisher = "Landes Bioscience",

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T1 - The NFκB inhibitor, SN50, induces differentiation of glioma stem cells and suppresses their oncogenic phenotype

AU - Zhang, Li

AU - Ren, Xingcong

AU - Cheng, Yan

AU - Liu, Xiuping

AU - Allen, Joshua E.

AU - Zhang, Yi

AU - Yuan, Yunsheng

AU - Huang, Siu Yuan

AU - Yang, Weiwei

AU - Berg, Arthur

AU - Webb, Becky S.

AU - Connor, James

AU - Liu, Chang Gong

AU - Lu, Zhimin

AU - El-Deiry, Wafik S.

AU - Yang, Jin Ming

N1 - Funding Information: Supported by grants from the US Public Health Service CA135038, the National Natural Sciences Foundation of China (81101913), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

PY - 2014/5

Y1 - 2014/5

N2 - The malignant phenotype of glioblastoma multiforme (GBM) is believed to be largely driven by glioma stem-like cells (GSCs), and targeting GSCs is now considered a promising new approach to treatment of this devastating disease. Here, we show that SN50, a cell-permeable peptide inhibitor of NFκB, induced robust differentiation of human GSCs, causing loss of their oncogenic potential. We observed that following treatment of GSCs with SN50, their differentiated progeny cells showed significant decreases in their capability to form neuro-spheres and to invade in vitro and a reduction in their tumorigenicity in mouse xenograft models, but had increased sensitivity to the chemotherapeutic drug temozolomide and to radiation treatment. These results suggest that blocking the NFκB pathway may be explored as a useful mean to induce differentiation of GSCs, and provide another supportive evidence for the promise of differentiation therapy in treatment of malignant brain tumors.

AB - The malignant phenotype of glioblastoma multiforme (GBM) is believed to be largely driven by glioma stem-like cells (GSCs), and targeting GSCs is now considered a promising new approach to treatment of this devastating disease. Here, we show that SN50, a cell-permeable peptide inhibitor of NFκB, induced robust differentiation of human GSCs, causing loss of their oncogenic potential. We observed that following treatment of GSCs with SN50, their differentiated progeny cells showed significant decreases in their capability to form neuro-spheres and to invade in vitro and a reduction in their tumorigenicity in mouse xenograft models, but had increased sensitivity to the chemotherapeutic drug temozolomide and to radiation treatment. These results suggest that blocking the NFκB pathway may be explored as a useful mean to induce differentiation of GSCs, and provide another supportive evidence for the promise of differentiation therapy in treatment of malignant brain tumors.

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The NFκB inhibitor, SN50, induces differentiation of glioma stem cells and suppresses their oncogenic phenotype

Abstract

Keywords

ASJC Scopus subject areas

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