PMID- 18989978
OWN - NLM
STAT- MEDLINE
DCOM- 20111129
LR  - 20181113
IS  - 1520-6025 (Electronic)
IS  - 0163-3864 (Print)
IS  - 0163-3864 (Linking)
VI  - 71
IP  - 11
DP  - 2008 Nov
TI  - Molecular-targeted antitumor agents. 19. Furospongolide from a marine 
      Lendenfeldia sp. sponge inhibits hypoxia-inducible factor-1 activation in breast 
      tumor cells.
PG  - 1854-60
LID - 10.1021/np800342s [doi]
AB  - A natural product chemistry-based approach was employed to discover 
      small-molecule inhibitors of the important tumor-selective molecular target 
      hypoxia-inducible factor-1 (HIF-1). Bioassay-guided isolation of an active lipid 
      extract of a Saipan collection of the marine sponge Lendenfeldia sp. afforded the 
      terpene-derived furanolipid furospongolide as the primary inhibitor of 
      hypoxia-induced HIF-1 activation (IC(50) 2.9 muM, T47D breast tumor cells). The 
      active component of the extract also contained one new cytotoxic scalarane 
      sesterterpene and two previously reported scalaranes. Furospongolide blocked the 
      induction of the downstream HIF-1 target secreted vascular endothelial growth 
      factor (VEGF) and was shown to suppress HIF-1 activation by inhibiting the 
      hypoxic induction of HIF-1alpha protein. Mechanistic studies indicate that 
      furospongolide inhibits HIF-1 activity primarily by suppressing tumor cell 
      respiration via the blockade of NADH-ubiquinone oxidoreductase (complex 
      I)-mediated mitochondrial electron transfer.
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, 
      USA.
FAU - Liu, Rui
AU  - Liu R
FAU - Mao, Shui-Chun
AU  - Mao SC
FAU - Morgan, J Brian
AU  - Morgan JB
FAU - Jekabsons, Mika B
AU  - Jekabsons MB
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  - R56 CA098787-05A1/CA/NCI NIH HHS/United States
GR  - R56 CA098787/CA/NCI NIH HHS/United States
GR  - R01 CA098787-04/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
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20081106
PL  - United States
TA  - J Nat Prod
JT  - Journal of natural products
JID - 7906882
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Furans)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (furospongolide)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/chemistry/*isolation & purification/*pharmacology
MH  - Breast Neoplasms/metabolism
MH  - Drug Screening Assays, Antitumor
MH  - Female
MH  - Furans/chemistry/*isolation & purification/*pharmacology
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*antagonists & inhibitors
MH  - Marine Biology
MH  - Molecular Structure
MH  - Porifera/*chemistry
MH  - Vascular Endothelial Growth Factor A/drug effects
PMC - PMC2893247
MID - NIHMS86561
EDAT- 2008/11/08 09:00
MHDA- 2011/12/13 00:00
PMCR- 2010/06/28
CRDT- 2008/11/08 09:00
PHST- 2008/11/08 09:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
PHST- 2008/11/08 09:00 [entrez]
PHST- 2010/06/28 00:00 [pmc-release]
AID - 10.1021/np800342s [doi]
PST - ppublish
SO  - J Nat Prod. 2008 Nov;71(11):1854-60. doi: 10.1021/np800342s. Epub 2008 Nov 6.