NDLI: An inhibitor of arachidonate 5-lipoxygenase, Nordy, induces differentiation and inhibits self-renewal of glioma stem-like cells.

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Year: 2011 Volume: 7 Issue: 1

An inhibitor of arachidonate 5-lipoxygenase, Nordy, induces differentiation and inhibits self-renewal of glioma stem-like cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Wang, Bin Yu, Shi-cang Jiang, Jian-yong Porter, Gavin Wallace Zhao, Lin-tao Wang, Zhe Tan, Hong Cui, You-hong Qian, Cheng Ping, Yi-fang Bian, Xiu-wu
Description	Country affiliation: China Author Affiliation: Wang B ( Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.)
Abstract	Recent progress in cancer biology indicates that eradication of cancer stem cells (CSCs) is essential for more effective cancer therapy. Unfortunately, cancer stem cells such as glioma stem-like cells (GSLCs) are often resistant to either radio- or chemotherapy. Therefore, screening and development for novel therapeutic modalities against CSCs has been an important emerging field in cancer research. In this study, we report that a synthetic dl-nordihydroguaiaretic acid compound (dl-NDGA or 'Nordy'), inhibited self-renewal and induced differentiation of GSLCs in vitro and in vivo. We found that Nordy inhibited an enzyme known to be involved in leukemia stem cell and leukemia progression, Alox-5, and attenuated the growth of GSLCs in vitro. Nordy reduced the GSLC pool through a decrease in the CD133(+) population and abrogated clonogenicity. Nordy appeared to exert its effect via astrocytic differentiation by up-regulation of GFAP and down-regulation of stemness related genes, rather than by inducing apoptosis of GSLCs. The growth inhibition of xenografted glioma by Nordy was more long-lasting compared with that of the akylating agent BCNU, which exhibited significant relapse on drug discontinuation resulting from an enrichment of GSLCs. Meanwhile, transient exposure to Nordy reduced tumorigenecity of GSLCs and induced differentiation of the xenografts. Taken together, we have identified Alox-5 as a novel target in GSLCs and its inhibition with Nordy exhibits therapeutic implications through inducing GSLC differentiation.
File Format	HTM / HTML
ISSN	15508943
Issue Number	2
Volume Number	7
Journal	Stem Cell Reviews and Reports
e-ISSN	15586804
Language	English
Publisher	Springer
Publisher Date	2011-06-01
Publisher Place	United States
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Cell Biology Arachidonate 5-lipoxygenase Metabolism Cell Differentiation Drug Effects Cell Proliferation Glioma Pathology Lipoxygenase Inhibitors Pharmacology Masoprocol Analogs & Derivatives Neoplastic Stem Cells Animals Antigens, Cd Astrocytes Cell Cycle Cell Line, Tumor Female Glial Fibrillary Acidic Protein Glycoproteins Homeodomain Proteins Humans Intermediate Filament Proteins Ki-67 Antigen Leukotriene B4 Mice Mice, Nude Neoplasm Transplantation Enzymology Nerve Tissue Proteins Nestin Octamer Transcription Factor-3 Peptides Protein-serine-threonine Kinases Soxb1 Transcription Factors Transplantation, Heterologous Tumor Burden Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Medicine

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An Inhibitor of Arachidonate 5-Lipoxygenase, Nordy, Induces Differentiation and Inhibits Self-Renewal of Glioma Stem-Like Cells

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An inhibitor of arachidonate 5-lipoxygenase, Nordy, induces differentiation and inhibits self-renewal of glioma stem-like cells.

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An Inhibitor of Arachidonate 5-Lipoxygenase, Nordy, Induces Differentiation and Inhibits Self-Renewal of Glioma Stem-Like Cells

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An inhibitor of arachidonate 5-lipoxygenase, Nordy, induces differentiation and inhibits self-renewal of glioma stem-like cells.