PMID- 21240677
OWN - NLM
STAT- MEDLINE
DCOM- 20110623
LR  - 20220318
IS  - 1861-0293 (Electronic)
IS  - 1340-3443 (Linking)
VI  - 65
IP  - 2
DP  - 2011 Apr
TI  - Red ginseng deregulates hypoxia-induced genes by dissociating the HIF-1 dimer.
PG  - 344-52
LID - 10.1007/s11418-010-0504-8 [doi]
AB  - 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-1alpha 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.
FAU - Choi, Yong-Joon
AU  - Choi YJ
AD  - Department of Pharmacology, Ischemic/Hypoxic Disease Institute, Seoul National 
      University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Korea.
FAU - Choi, Hyunsung
AU  - Choi H
FAU - Cho, Chung-Hyun
AU  - Cho CH
FAU - Park, Jong-Wan
AU  - Park JW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110118
PL  - Japan
TA  - J Nat Med
JT  - Journal of natural medicines
JID - 101518405
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Plant Extracts)
RN  - 138391-32-9 (Aryl Hydrocarbon Receptor Nuclear Translocator)
SB  - IM
MH  - Aryl Hydrocarbon Receptor Nuclear Translocator/metabolism
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/*metabolism
MH  - Immunoblotting
MH  - Immunoprecipitation
MH  - Panax/*chemistry
MH  - Plant Extracts/chemistry/*pharmacology
MH  - Protein Binding/drug effects
MH  - Protein Multimerization/drug effects
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2011/01/18 06:00
MHDA- 2011/06/24 06:00
CRDT- 2011/01/18 06:00
PHST- 2010/09/23 00:00 [received]
PHST- 2010/12/21 00:00 [accepted]
PHST- 2011/01/18 06:00 [entrez]
PHST- 2011/01/18 06:00 [pubmed]
PHST- 2011/06/24 06:00 [medline]
AID - 10.1007/s11418-010-0504-8 [doi]
PST - ppublish
SO  - J Nat Med. 2011 Apr;65(2):344-52. doi: 10.1007/s11418-010-0504-8. Epub 2011 Jan 
      18.