Unique proteomic features induced by a potential antiglioma agent, Nordy (dl-nordihydroguaiaretic acid), in glioma cells.
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.
Bian
Xiu-Wu
XW
Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing, China. bianxiuwu@263.net
Xu
Jian-Ping
JP
Ping
Yi-Fang
YF
Wang
Yan
Y
Chen
Jian-Hong
JH
Xu
Cheng-Ping
CP
Wu
Yu-Zhang
YZ
Wu
Jun
J
Zhou
Xiang-Dong
XD
Chen
Yi-Sheng
YS
Shi
Jing-Quan
JQ
Wang
Ji Ming
JM
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009637:Masoprocol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D016859:Lipoxygenase Inhibitors; C510003:nordy; D009637:Masoprocol