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The anti-cancer compound Nordy inhibits CXCR4-mediated production of IL-8 and VEGF by malignant human glioma cells

  • Lab Investigation-Human/Animal tissue
  • Published:
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Abstract

The chemokine receptor CXCR4 plays an important role in tumor growth, angiogenesis and metastasis. Our previous studies showed that Nordy, a synthetic chiral compound of nordihydroguaiaretic acid, inhibited the growth and angiogenesis of various malignant tumors. In this study we examined the capacity of Nordy to regulate CXCR4–mediated production of angiogenic factors by human glioblastoma cells. We found that Nordy potently inhibited CXCR4 ligand SDF-1-induced production of IL-8 and vascular endothelial cell growth factor, two important angiogenic factors implicated in the progression of malignant tumors. Further study revealed that the effect of Nordy was attributable to its down-regulation of the expression of functional CXCR4 in glioblastoma cells. These results suggest that the anti-cancer activity of Nordy is due, at least in part, to its suppression of the chemokine receptor CXCR4 thus reducing the production of angiogenic factors by tumor cells.

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Acknowledgments

This study was supported by grants from National Natural Science Foundation of China (NSFC, No. 30370552), National High Technology Project of China (No. 2002AA001010) and Key Project of Chongqing Science and Technology Committee (CSTC-2005AA5007).

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Authors and Affiliations

  1. Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China

    Yi-fang Ping, Xiao-hong Yao, Jian-hong Chen, Hong Liu, Dai-lun Chen & Xiu-wu Bian

  2. Department of Pharmacy, Division of Basic Medical Science, Third Military Medical University, Chongqing, 400038, China

    Xiang-dong Zhou

  3. Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, 21702, USA

    Ji Ming Wang

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  1. Yi-fang Ping
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  2. Xiao-hong Yao
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Correspondence to Xiu-wu Bian.

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Y.-F. Ping, X.-H. Yao, and J.-H. Chen contributed equally to the study.

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Ping, Yf., Yao, Xh., Chen, Jh. et al. The anti-cancer compound Nordy inhibits CXCR4-mediated production of IL-8 and VEGF by malignant human glioma cells. J Neurooncol 84, 21–29 (2007). https://doi.org/10.1007/s11060-007-9349-8

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  • DOI: https://doi.org/10.1007/s11060-007-9349-8

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