Momordin I, a compound of ampelopsis radix, inhibits AP-1 activation induced by phorbol ester.
Recently, we reported that momordin I from Ampelopsis radix is an activator protein-1 (AP-1) function inhibitor. Mormordin I showed both inhibition of AP-1 transcriptional activity and cellular cytotoxicity. Moreover, its inhibitory action was also identified in the animal experiments. The present study attempted to determine the mechanism of the action of momordin I more clearly. In mouse fibroblast cells, momordin I suppressed the AP-1 activity induced by phorbol 12-myristate 13-acetate (PMA), as well as blocked the de novo synthesis of AP-1 protein. Momordin I also showed cell cytotoxic activities on various cell lines and blocked the uptake of [(3)H]thymidine in cell proliferation induced by PMA. From these results, the inhibitory action of momordin I on AP-1 was clearly identified. Through the competitive binding assays, it appears that the inhibitory site of momordin I might be in the Jun/Fos dimer, and not in the DNA. Momordin I also showed the inhibitory action on the Jun/Jun homodimer, as well as on the Jun/Fos heterodimer. It also inhibited the autoregulated de novo synthesis of AP-1 by the Jun/Jun homodimer. In addition, since the truncated AP-1 used in this study only has the bZip regions of c-Jun and c-Fos, it appears that the inhibitory action site of momordin I may be the basic region of c-Jun instead of on the same region of c-Fos.
Park
S
S
Department of Chemistry, College of Natural Science, Seoul National University, Seoul, South Korea.
Lee
D K
DK
Whang
Y H
YH
Yang
C H
CH
D016475:3T3 Cells; D000818:Animals; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051379:Mice; D009828:Oleanolic Acid / Q000031:analogs & derivatives; D010944:Plants / Q000737:chemistry*; D016755:Proto-Oncogene Proteins c-jun / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000235:genetics
D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D012503:Saponins; D018808:Transcription Factor AP-1; C408362:momordin I (Oleanolic Acid); D009828:Oleanolic Acid; D013755:Tetradecanoylphorbol Acetate