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Nordy (dl‐nordihydroguaiaretic acid) Inhibits the Growth of Malignant Human Glioma by Attenuating Formylpeptide Receptor‐mediated Signaling
Author(s) -
Chen Jianhong,
Yao Xiaohong,
Gong Wanghua,
Wang Ji Ming,
Bian Xiuwu
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb89
Subject(s) - nordihydroguaiaretic acid , chemotaxis , chemistry , microbiology and biotechnology , glioma , signal transduction , receptor , cancer research , biology , biochemistry , lipoxygenase , enzyme
Nordy is a chiral compound synthesized based on the structure of a natural lipoxygenase (LO) inhibitor nordihydroguaiaretic acid (NDGA) from plants. We found that Nordy, in a non‐cytotoxic concentration range, potently inhibited the chemotaxis and calcium flux of a human glioblastoma cell line U87 induced by a formylpeptide receptor (FPR) agonist, formyl‐methionyl‐leucyl‐phenylalanine (fMLF) and epidermal growth factor (EGF). U87 cells treated by Nordy also showed a significantly impaired proliferation and expression of mRNA for vascular endothelial growth factor (VEGF) induced by fMLF. The chemotactic and proliferation responses of Nordy treated U87 cells to EGF were concomitantly diminished. Nordy did not significantly affect FPR gene expression in U87 cells, but attenuated the activation of a plethora of signaling molecules including ERK1/2, p38, JNK, and Akt when the cells were stimulated by fMLF. EGF‐induced EGF receptor phosphorylation was also inhibited in Nordy‐treated U87 cells. Moreover, Nordy significantly reduced the tumorigenicity of U87 cells in nude mice. Our results suggest that Nordy is capable of inhibiting glioma cell responses to signals that promote cell motility, growth and production of VEGF. Thus, Nordy may constitute a molecular basis for the development of novel anti‐cancer drugs.