PMID- 19921787
OWN - NLM
STAT- MEDLINE
DCOM- 20100119
LR  - 20211020
IS  - 1520-6025 (Electronic)
IS  - 0163-3864 (Print)
IS  - 0163-3864 (Linking)
VI  - 72
IP  - 12
DP  - 2009 Dec
TI  - The Caulerpa pigment caulerpin inhibits HIF-1 activation and mitochondrial 
      respiration.
PG  - 2104-9
LID - 10.1021/np9005794 [doi]
AB  - The transcription factor hypoxia-inducible factor-1 (HIF-1) represents an 
      important molecular target for anticancer drug discovery. In a T47D cell-based 
      reporter assay, the Caulerpa spp. algal pigment caulerpin (1) inhibited 
      hypoxia-induced as well as 1,10-phenanthroline-induced HIF-1 activation. The 
      angiogenic factor vascular endothelial growth factor (VEGF) is regulated by 
      HIF-1. Caulerpin (10 microM) suppressed hypoxic induction of secreted VEGF 
      protein and the ability of hypoxic T47D cell-conditioned media to promote tumor 
      angiogenesis in vitro. Under hypoxic conditions, 1 (10 microM) blocked the 
      induction of HIF-1alpha protein, the oxygen-regulated subunit that controls HIF-1 
      activity. Reactive oxygen species produced by mitochondrial complex III are 
      believed to act as a signal of cellular hypoxia that leads to HIF-1alpha protein 
      induction and activation. Further mechanistic studies revealed that 1 inhibits 
      mitochondrial respiration at electron transport chain (ETC) complex I 
      (NADH-ubiquinone oxidoreductase). Under hypoxic conditions, it is proposed that 1 
      may disrupt mitochondrial ROS-regulated HIF-1 activation and HIF-1 downstream 
      target gene expression by inhibiting the transport or delivery of electrons to 
      complex III.
FAU - Liu, Yang
AU  - Liu Y
AD  - Department of Pharmacognosy and Research Institute of Pharmaceutical Sciences, 
      School of Pharmacy, University of Mississippi, University, Mississippi 38677, and 
      Department of Biology, University of Mississippi, University, Mississippi 38677.
FAU - Morgan, J Brian
AU  - Morgan JB
FAU - Coothankandaswamy, Veena
AU  - Coothankandaswamy V
FAU - Liu, Rui
AU  - Liu R
FAU - Jekabsons, Mika B
AU  - Jekabsons MB
FAU - Mahdi, Fakhri
AU  - Mahdi F
FAU - Nagle, Dale G
AU  - Nagle DG
FAU - Zhou, Yu-Dong
AU  - Zhou YD
LA  - eng
GR  - P20 RR021929-04/RR/NCRR NIH HHS/United States
GR  - R01 CA098787-05A2/CA/NCI NIH HHS/United States
GR  - NA16RU1496/PHS HHS/United States
GR  - C06 RR014503/RR/NCRR NIH HHS/United States
GR  - CA98787/CA/NCI NIH HHS/United States
GR  - P20RR021929/RR/NCRR NIH HHS/United States
GR  - P20 RR021929/RR/NCRR NIH HHS/United States
GR  - C06 RR-14503-01/RR/NCRR NIH HHS/United States
GR  - R01 CA098787/CA/NCI NIH HHS/United States
GR  - R56 CA098787/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Nat Prod
JT  - Journal of natural products
JID - 7906882
RN  - 0 (Coloring Agents)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Indoles)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 26612-48-6 (caulerpin)
RN  - EC 7.1.1.2 (Electron Transport Complex I)
SB  - IM
MH  - Caulerpa/*chemistry
MH  - Coloring Agents/chemistry/pharmacology
MH  - Electron Transport Complex I/antagonists & inhibitors
MH  - Female
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/*drug effects
MH  - Indoles/chemistry/isolation & purification/*pharmacology
MH  - Mitochondria/drug effects/metabolism
MH  - Molecular Structure
MH  - Vascular Endothelial Growth Factor A/metabolism
PMC - PMC2798910
MID - NIHMS160715
EDAT- 2009/11/20 06:00
MHDA- 2010/01/20 06:00
PMCR- 2010/12/01
CRDT- 2009/11/20 06:00
PHST- 2009/11/20 06:00 [entrez]
PHST- 2009/11/20 06:00 [pubmed]
PHST- 2010/01/20 06:00 [medline]
PHST- 2010/12/01 00:00 [pmc-release]
AID - 10.1021/np9005794 [doi]
PST - ppublish
SO  - J Nat Prod. 2009 Dec;72(12):2104-9. doi: 10.1021/np9005794.