Red ginseng deregulates hypoxia-induced genes by dissociating the HIF-1 dimer.
Water extract of Korean red ginseng (KRGW) contains numerous bioactive ginsenosides and is very popular as a multi-purpose medicine for health improvement. KRGW has been in the limelight because of its clinical benefit in cancer control. A growing body of evidence suggests that hypoxia-inducible factor-1 (HIF-1) plays critical roles in tumor promotion under hypoxia and that it is a compelling target for cancer therapy. In this paper we investigated the effect of KRGW on HIF-1-mediated adaptation to hypoxia. In both Hep3B cancer and HEK293 immortalized normal cell lines, KRGW attenuated the expression of hypoxia-induced genes without apparent cytotoxicity. Mechanistically, KRGW did not affect the synthesis, degradation, and translocation of HIF-1 in hypoxia. Interestingly, KRGW was found to repress the transcriptional activity of HIF-1 by interfering with the dimerization between HIF-1α and aryl hydrocarbon receptor nuclear translocator. To identify the HIF-inhibiting ingredient(s), we examined the effects of major ginsenosides on HIF-1 activity, but all ginsenosides tested failed to inactivate HIF-1. Based on these results, we propose that HIF-1 inhibition underlies the anticancer effect of ginseng. It is also proposed that KRGW could be an anticancer drug targeting hypoxic tumors.
Department of Pharmacology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Korea.
Yong-Joon
YJ
Choi
Hyunsung
H
Choi
Chung-Hyun
CH
Cho
Jong-Wan
JW
Park
D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D015151:Immunoblotting; D047468:Immunoprecipitation; D005894:Panax / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction
D051793:Hypoxia-Inducible Factor 1; D010936:Plant Extracts; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator
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