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Unique proteomic features induced by a potential antiglioma agent, Nordy ( dl ‐nordihydroguaiaretic acid), in glioma cells
Author(s) -
Bian XiuWu,
Xu JianPing,
Ping YiFang,
Wang Yan,
Chen JianHong,
Xu ChengPing,
Wu YuZhang,
Wu Jun,
Zhou XiangDong,
Chen YiSheng,
Shi JingQuan,
Wang Ji Ming
Publication year - 2008
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200700054
Subject(s) - glioma , nordihydroguaiaretic acid , biology , cell culture , cell growth , microbiology and biotechnology , proteome , biochemistry , cancer research , enzyme , genetics , arachidonic acid
Nordy is a chirally synthesized compound of a natural lipoxygenase inhibitor nordihydroguaiaretic acid. In this study, we found that Nordy inhibited the growth of human glioma cell lines in vitro and their tumorigenicity in mice. In addition, Nordy promoted differentiation of highly malignant human glioma cells. Investigation into the mechanistic basis of Nordy activities revealed that it altered the pattern of protein expression profiles in tumor cells. By using 2‐DE, we found that in human glioma cell lines, at least six proteins were down‐regulated after Nordy treatment, while four proteins were elevated in the same cells. Among the six down‐regulated proteins, microsequencing with MALDI TOF MS confirmed the identity of five: proliferation‐associated gene A (PAG‐A), alternative splicing factor‐3 (ASF‐3), β‐galactoside binding lectin, eukaryotic translation initiation factor 5A (eIF‐5A), and coffilin‐1 (nonmuscle). Four up‐regulated proteins were GST‐π, glyceraldehyde‐3‐phosphate dehydrogenase, α‐enolase, and cyclophilin. All these proteins have been reported to participate in key cellular functions including proliferation, metabolism, differentiation, apoptosis, and gene transcription. Our results suggest that Nordy may constitute a promising drug lead for the development of novel antitumor agents targeting proteins that control tumor cell function at multiple levels.