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Unique proteomic features induced by a potential anti‐glioma agent, Nordy (dl‐nordihydroguaiaretic acid), in glioma cells
Author(s) -
Bian Xiuwu,
Xu Jianping,
Chen Jianhong,
Wang Ji Ming
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.lb88-c
Subject(s) - glioma , biology , nordihydroguaiaretic acid , microbiology and biotechnology , cell culture , biochemistry , chemistry , 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‐D electrophoresis, we found that in human glioma cell lines, at least 6 proteins were down‐regulated after Nordy‐treatment, while 4 proteins were elevated in the same cells. Among 6 down‐regulated proteins, micro‐sequencing with matrix assisted laser desorption ionization time of flight mass specrtrometry confirmed the identity of 5: 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 (non‐muscle). Four up‐regulated proteins were glutathione S‐transferase 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 anti‐tumor agents targeting proteins that control tumor cell function at multiple levels.