Unique proteomic features induced by a potential antiglioma agent, Nordy (<scp>dl</scp>‐nordihydroguaiaretic acid), in glioma cells

Bian, Xiu‐Wu; Xu, Jun; Ping, Yi‐Fang; Wang, Yan; Chen, Jianhong; Xu, Chunfang; Wu, Yuzhang; Wu, Jun; Zhou, Xiangdong; Chen, Yisheng; Shi, Jing; Wang, Ji Ming

doi:10.1002/pmic.200700054

Cited by 15 publications

(16 citation statements)

References 34 publications

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“…In our previous studies, we found Nordy treatment repressed growth of glioma cells in vitro and in vivo [6,7], but the present findings suggest growth inhibition of GSLCs could be occurring. We then asked whether Nordy treatment might target glioma cells as a whole or target GSLCs preferentially.…”

Section: Alox-5 Is Preferentially Expressed By Gslcs and Is Inhibitedcontrasting

confidence: 78%

“…In our previous study, we revealed inhibition of glioma growth by Nordy treatment [7], but the mechanistic basis of such anti-glioma activity is largely unknown. In light of enhanced expression of Alox-5 in GSLCs, we tested whether Nordy, the racemate of a lipoxygenase inhibitor NDGA, could inhibit the enzymatic activity of Alox-5 in an in vitro assay system.…”

Section: Alox-5 Is Preferentially Expressed By Gslcs and Is Inhibitedmentioning

confidence: 99%

“…Nordy (dl-nordihydroguaiaretic acid, dl-NDGA) is a synthetic compound which has demonstrated anti-tumor activity [6,7]. Furthermore, the anti-tumor effect of Nordy was found to be mediated by its regulatory roles in differentiation induction and growth inhibition of glioma cells both in vitro and in vivo using a proteomic approach [7].…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, the anti-tumor effect of Nordy was found to be mediated by its regulatory roles in differentiation induction and growth inhibition of glioma cells both in vitro and in vivo using a proteomic approach [7]. However, a distinct cellular target for Nordy has yet to be identified.…”

Section: Introductionmentioning

confidence: 99%

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

Wang

Jian-yong

et al. 2010

Stem Cell Rev and Rep

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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.

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Section: Alox-5 Is Preferentially Expressed By Gslcs and Is Inhibitedcontrasting

confidence: 78%

Section: Alox-5 Is Preferentially Expressed By Gslcs and Is Inhibitedmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Wang

Jian-yong

et al. 2010

Stem Cell Rev and Rep

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“…Besides, EIF5A plays an important role in hepatocellular carcinoma (HCC) tumorigenesis, and targeting EIF5A may offer new therapeutic alternatives to hepatocellular carcinoma patients [28]. In glioma, EIF5A was downregulated after Nordy treatment [29].…”

Section: Discussionmentioning

confidence: 99%

The effect of miR‐7 on behavior and global protein expression in glioma cell lines

Liu

Yao

et al. 2011

Electrophoresis

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Malignant glioma is a common cancer of the nervous system. Despite recent research efforts in cancer therapy, the prognosis of patients with malignant glioma has remained dismal. MicroRNAs are noncoding RNAs that inhibit the expression of their targets in a sequence-specific manner, and a few have been shown to act as oncogenes or tumor suppressors. Here, we aimed at exploring the precise biological role of microRNA-7 (miR-7) and the global protein changes in glioma cell lines transiently transfected with miR-7. Transfection of miR-7 into glioma cell lines causes inhibition of cell migration and invasion and suppression of tumorigenesis. Moreover, ectopic expression of miR-7 inhibits lung metastases of glioma in vivo. Among 65 protein spots with differential expression separated by 2-DE, 37 proteins were successfully identified by MS/MS analysis. Of those, the 25 downregulated proteins, which include 14-3-3ζ, eukaryotic translation initiation factor 5A (EIF5A), and annexin A4, may be downstream targets of miR-7, a finding that could elucidate some aspects of the behavior of glioma cells at the protein level. In conclusion, the absence of miR-7 function could cause downstream molecules to switch on or off, resulting in glioma development, invasion, and metastases. MiR-7-based gene treatment may be a novel anti-invasion therapeutic strategy for malignant glioma.

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Prognostic significance and therapeutic potential of eukaryotic translation initiation factor 5A (eIF5A) in hepatocellular carcinoma

Lee

Tsang

Shek

et al. 2010

Intl Journal of Cancer

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Using comparative proteomic and genomic approaches, the authors identified eukaryotic translation initiation factor 5A (eIF5A) as an oncofetal molecule highly abundant in mouse embryonic livers and human hepatocellular carcinoma (HCC) cell lines. To evaluate the oncogenic role and prognostic significance of eIF5A in HCC, we investigate the expression patterns of the two isoforms (eIF5A1 and eIF5A2) in a cohort of 258 HCC cases by cDNA microarray. Both eIF5A isoforms were expressed in the tumors, and clinically correlated eIF5A1 with more numbers of tumor nodules and eIF5A2 with tumor venous infiltration in HCC. In a separate cohort of 50 HCCs, high level of eIF5A2, but not eIF5A1, was associated with elevated levels of deoxyhypusine synthase and deoxyhypusine hydroxylase that catalyze post-translational hypusination of eIF5A protein.Interestingly, N1-guanyl-1,7-diaminoheptane (GC7), which is an inhibitor for the first step of eIF5A hypusination, was shown to significantly impair the cell proliferation and invasion of primary HCC cells (HepG2 and Hep3B). To further demonstrate the tumorigenic role associated with eIF5A, a drastic reduction of cell proliferation was associated with suppression of eIF5A2 by transfecting Hep3B, H2-P and H2-M HCC cells expressing high level of this isoform using small interfering RNA (siRNA) against eIF5A2. For these assays, a milder response was usually observed in normal hepatocyte cell line. Therefore, these findings suggest that eIF5A plays an important role in HCC tumorigenesis and metastasis, and targeting eIF5A hypusination by GC7 inhibitor or eIF5A2 by RNA interference (RNAi) may offer new therapeutic alternatives to HCC patients.Eukaryotic translation initiation factor 5A (eIF5A) is one of the several identified eukaryotic translation initiation factors (eIFs). However, it differs from other eIFs in that it has a polyamine-derived amino acid, hypusine/N e -(4-amino-2-hydroxy-butyl)lysine, in its primary structure. Because eIF5A is synthesized initially as an inactive precursor, post-translational modification of hypusination is required to convert it to its active form. This modification is unique because it involves two sequential enzymatic steps that are catalyzed by deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH). 1-3 eIF5A protein is present in the cytoplasm associating with the endoplasmic reticulum, 4 and also found in the nucleus largely attributed to the nuclear localization signal at the amino-terminal sequence of the protein. 5 A recent study also demonstrates the effects of hypusination in defining the cellular localizations of non-hypusinated and hypusinated eIF5A. The precursor of eIF5A is found in both cytoplasm and nucleus and the mature one is restricted largely in the cytoplasm. 6 The amino acid sequence of eIF5A is highly conserved in mammals 1 and two isoforms of eIF5A, namely eIF5A1 and eIF5A2, have been identified. Because each shows a differential expression pattern in a panel of human cancer cell lines, Clement and others have implica...

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Unique proteomic features induced by a potential antiglioma agent, Nordy (dl‐nordihydroguaiaretic acid), in glioma cells

Cited by 15 publications

References 34 publications

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

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

The effect of miR‐7 on behavior and global protein expression in glioma cell lines

Prognostic significance and therapeutic potential of eukaryotic translation initiation factor 5A (eIF5A) in hepatocellular carcinoma

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