PMID- 15620241
OWN - NLM
STAT- MEDLINE
DCOM- 20050310
LR  - 20181113
IS  - 0163-3864 (Print)
IS  - 1520-6025 (Electronic)
IS  - 0163-3864 (Linking)
VI  - 67
IP  - 12
DP  - 2004 Dec
TI  - Laurenditerpenol, a new diterpene from the tropical marine alga 
      Laurenciaintricata that potently inhibits HIF-1 mediated hypoxic signaling in 
      breast tumor cells.
PG  - 2002-7
AB  - The degree of tumor hypoxia correlates with advanced disease stages and treatment 
      resistance. The transcription factor hypoxia-inducible factor-1 (HIF-1) promotes 
      tumor cell adaptation and survival under hypoxic conditions. Therefore, specific 
      HIF-1 inhibitors represent an important new class of potential tumor-selective 
      therapeutic agents. A T47D human breast tumor cell-based reporter assay was used 
      to examine extracts of plants and marine organisms for inhibitors of HIF-1 
      activation. Bioassay-guided fractionation of the lipid extract of the red alga 
      Laurencia intricata yielded a structurally novel diterpene, laurenditerpenol (1). 
      The structure of 1 was determined spectroscopically. The relative configurations 
      of the substituents of each ring system were assigned on the basis of NOESY 
      correlations. The absolute configuration of position C-1 was determined by the 
      modified Mosher ester procedure (directly in NMR tubes). Compound 1 potently 
      inhibited hypoxia-activated HIF-1 (IC50: 0.4 microM) and hypoxia-induced VEGF (a 
      potent angiogenic factor) in T47D cells. Compound 1 selectively inhibits HIF-1 
      activation by hypoxia but not iron chelator-induced activation. Further, 1 
      suppresses tumor cell survival under hypoxic conditions without affecting 
      normoxic cell growth. Compound 1 inhibits HIF-1 by blocking the induction of the 
      oxygen-regulated HIF-1alpha protein. Mitochondrial respiration studies revealed 
      that 1 suppresses oxygen consumption.
FAU - Mohammed, Kaleem A
AU  - Mohammed KA
AD  - Department of Pharmacognosy, National Center for Natural Products Research, and 
      Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of 
      Mississippi, University, Mississippi 38677-1848, USA.
FAU - Hossain, Chowdhury Faiz
AU  - Hossain CF
FAU - Zhang, Lei
AU  - Zhang L
FAU - Bruick, Richard K
AU  - Bruick RK
FAU - Zhou, Yu-Dong
AU  - Zhou YD
FAU - Nagle, Dale G
AU  - Nagle DG
LA  - eng
GR  - R01 CA098787/CA/NCI NIH HHS/United States
GR  - R01 CA098787-01A2/CA/NCI NIH HHS/United States
GR  - R56 CA098787/CA/NCI NIH HHS/United States
GR  - CA 98787-01/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Nat Prod
JT  - Journal of natural products
JID - 7906882
RN  - 0 (Antineoplastic Agents)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Diterpenes)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (laurenditerpenol)
SB  - IM
MH  - Antineoplastic Agents/chemistry/*isolation & purification/pharmacology
MH  - Breast Neoplasms
MH  - DNA-Binding Proteins/*antagonists & inhibitors
MH  - Diterpenes/chemistry/*isolation & purification/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - *Hypoxia
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Mitochondria/metabolism
MH  - Molecular Structure
MH  - Nuclear Magnetic Resonance, Biomolecular
MH  - Nuclear Proteins/*antagonists & inhibitors
MH  - Rhodophyta/*chemistry
MH  - Stereoisomerism
MH  - Transcription Factors/*antagonists & inhibitors
PMC - PMC2910713
MID - NIHMS216837
EDAT- 2004/12/29 09:00
MHDA- 2005/03/11 09:00
PMCR- 2010/07/27
CRDT- 2004/12/29 09:00
PHST- 2004/12/29 09:00 [pubmed]
PHST- 2005/03/11 09:00 [medline]
PHST- 2004/12/29 09:00 [entrez]
PHST- 2010/07/27 00:00 [pmc-release]
AID - 10.1021/np049753f [doi]
PST - ppublish
SO  - J Nat Prod. 2004 Dec;67(12):2002-7. doi: 10.1021/np049753f.