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Article: An inhibitor of arachidonate 5-lipoxygenase, Nordy, Induces differentiation and inhibits self-renewal of glioma stem-like cells

TitleAn inhibitor of arachidonate 5-lipoxygenase, Nordy, Induces differentiation and inhibits self-renewal of glioma stem-like cells
Authors
Issue Date2011
PublisherHumana Press, Inc.
Citation
Stem Cell Reviews and Reports, 2011, v. 7 n. 2, p. 458-470 How to Cite?
AbstractRecent 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.
Persistent Identifierhttp://hdl.handle.net/10722/143086
ISSN
2015 Impact Factor: 3.111
2015 SCImago Journal Rankings: 1.424
ISI Accession Number ID
Funding AgencyGrant Number
National Basic Research Program of China (973 Program)2010CB529403
national Natural Science Foundation of China (NSFC)30725035
30930103
Funding Information:

This work was supported by grants from the National Basic Research Program of China (973 Program, No. 2010CB529403) and the national Natural Science Foundation of China (NSFC Nos. 30725035 and 30930103).

 

DC FieldValueLanguage
dc.contributor.authorWang, Ben_US
dc.contributor.authorYu, SCen_US
dc.contributor.authorJiang, JYen_US
dc.contributor.authorPorter, GWen_US
dc.contributor.authorZhao, LTen_US
dc.contributor.authorWang, Zen_US
dc.contributor.authorTan, Hen_US
dc.contributor.authorCui, YHen_US
dc.contributor.authorQian, Cen_US
dc.contributor.authorPing, YFen_US
dc.contributor.authorBian, XWen_US
dc.date.accessioned2011-10-28T03:08:19Z-
dc.date.available2011-10-28T03:08:19Z-
dc.date.issued2011en_US
dc.identifier.citationStem Cell Reviews and Reports, 2011, v. 7 n. 2, p. 458-470en_US
dc.identifier.issn1550-8943-
dc.identifier.urihttp://hdl.handle.net/10722/143086-
dc.description.abstractRecent 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.-
dc.languageengen_US
dc.publisherHumana Press, Inc.en_US
dc.relation.ispartofStem Cell Reviews and Reportsen_US
dc.rightsThe original publication is available at www.springerlink.comen_US
dc.subject.meshArachidonate 5-Lipoxygenase - metabolism-
dc.subject.meshCell Proliferation - drug effects-
dc.subject.meshGlioma - pathology-
dc.subject.meshLipoxygenase Inhibitors - pharmacology-
dc.subject.meshNeoplastic Stem Cells - enzymology - pathology-
dc.titleAn inhibitor of arachidonate 5-lipoxygenase, Nordy, Induces differentiation and inhibits self-renewal of glioma stem-like cellsen_US
dc.typeArticleen_US
dc.identifier.emailPorter, GW: porterg@hku.hken_US
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1007/s12015-010-9175-9-
dc.identifier.pmid20809257-
dc.identifier.scopuseid_2-s2.0-79955015036-
dc.identifier.hkuros197274en_US
dc.identifier.volume7en_US
dc.identifier.issue2-
dc.identifier.spage458en_US
dc.identifier.epage470en_US
dc.identifier.isiWOS:000289297600021-
dc.publisher.placeUnited States-
dc.identifier.citeulike7783455-

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