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),
beta-galactoside binding lectin,
eukaryotic translation initiation factor 5A (eIF-5A), and coffilin-1 (nonmuscle). Four up-regulated
proteins were GST-pi,
glyceraldehyde-3-phosphate dehydrogenase,
alpha-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.