PMID- 17958397
OWN - NLM
STAT- MEDLINE
DCOM- 20080107
LR  - 20211020
IS  - 0163-3864 (Print)
IS  - 1520-6025 (Electronic)
IS  - 0163-3864 (Linking)
VI  - 70
IP  - 11
DP  - 2007 Nov
TI  - Molecular-targeted antitumor agents. 15. Neolamellarins from the marine sponge 
      Dendrilla nigra inhibit hypoxia-inducible factor-1 activation and secreted 
      vascular endothelial growth factor production in breast tumor cells.
PG  - 1741-5
AB  - The transcription factor hypoxia-inducible factor-1 (HIF-1) has emerged as a 
      major antitumor molecular target. Inhibition of HIF-1 activation has been shown 
      to suppress the growth, survival, and metastatic spread of hypoxic tumors. The 
      NCI Open Repository of marine invertebrates and algae lipid extracts was 
      evaluated for HIF-1 inhibitory activity in a T47D human breast tumor cell-based 
      reporter assay. Bioassay-guided chromatographic separation of the active extract 
      from the sponge Dendrilla nigra produced four new lamellarin-like phenolic 
      pyrroles, which most closely resemble the structure of the known D. cactos 
      compound lamellarin O. However, unlike lamellarins, the structures of 
      neolamellarin A (1), neolamellarin B (2), 5-hydroxyneolamellarin B (3), and 
      7-hydroxyneolamellarin A (4) lack the carboxyl moiety at position C-2 of the 
      substituted pyrrole ring and have a significantly different pattern of oxidation. 
      Compound 4 was found to inhibit hypoxia-induced HIF-1 activation (IC50 1.9 
      microM) in T47D cells. Hypoxic induction of vascular endothelial growth factor 
      (VEGF), a potent angiogenic factor and HIF-1 target gene, was also inhibited by 4 
      at the secreted protein level.
FAU - Liu, Rui
AU  - Liu R
AD  - Department of Pharmacognosy, Research Institute of Pharmaceutical Sciences, 
      School of Pharmacy, University of Mississippi, Mississippi 38677-1848, USA.
FAU - Liu, Yang
AU  - Liu Y
FAU - Zhou, Yu-Dong
AU  - Zhou YD
FAU - Nagle, Dale G
AU  - Nagle DG
LA  - eng
GR  - R01 CA098787-02/CA/NCI NIH HHS/United States
GR  - R01 CA098787-03/CA/NCI NIH HHS/United States
GR  - C06 RR014503/RR/NCRR NIH HHS/United States
GR  - CA98787/CA/NCI 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
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20071025
PL  - United States
TA  - J Nat Prod
JT  - Journal of natural products
JID - 7906882
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Heterocyclic Compounds, 4 or More Rings)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Vascular Endothelial Growth Factor A)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/chemistry/*isolation & purification/*pharmacology
MH  - Breast Neoplasms/metabolism
MH  - Drug Screening Assays, Antitumor
MH  - Female
MH  - Heterocyclic Compounds, 4 or More Rings/chemistry/*isolation & 
      purification/*pharmacology
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/*antagonists & inhibitors/genetics
MH  - Molecular Structure
MH  - National Cancer Institute (U.S.)
MH  - Porifera/*chemistry
MH  - Structure-Activity Relationship
MH  - United States
MH  - Vascular Endothelial Growth Factor A/*antagonists & inhibitors/metabolism
PMC - PMC2914556
MID - NIHMS216818
EDAT- 2007/10/26 09:00
MHDA- 2008/01/08 09:00
PMCR- 2010/08/03
CRDT- 2007/10/26 09:00
PHST- 2007/10/26 09:00 [pubmed]
PHST- 2008/01/08 09:00 [medline]
PHST- 2007/10/26 09:00 [entrez]
PHST- 2010/08/03 00:00 [pmc-release]
AID - 10.1021/np070206e [doi]
PST - ppublish
SO  - J Nat Prod. 2007 Nov;70(11):1741-5. doi: 10.1021/np070206e. Epub 2007 Oct 25.