PMID- 20622986
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211020
IS  - 1568-7767 (Print)
IS  - 1572-980X (Electronic)
IS  - 1568-7767 (Linking)
VI  - 8
IP  - 2
DP  - 2009 Jun
TI  - Marine Natural Products as Inhibitors of Hypoxic Signaling in Tumors.
PG  - 415-429
AB  - Marine natural products have become a major source of new chemical entities in 
      the discovery of potential anticancer agents that potently suppress various 
      antitumor molecular targets. As a consequence of insufficient vascularization, 
      hypoxic regions form within rapidly growing solid tumor masses. Specific 
      alterations of gene expression in these hypoxic tumor cells help facilitate the 
      survival and metastatic spread of solid tumors. The transcriptional response to 
      cellular hypoxia is primarily mediated by the transcription factor 
      hypoxia-inducible factor-1 (HIF-1) that regulates the expression of more than 100 
      genes involved in cellular adaptation and survival under hypoxic stress. Clinical 
      studies in cancer patients indicate that HIF-1 activation is directly correlated 
      with advanced disease stages and treatment resistance. HIF-1 has emerged as an 
      important tumor-selective molecular target for anticancer drug discovery. As a 
      result, natural product-based inhibitors of HIF-1 activation have been identified 
      from plants and microorganisms. Recently, structurally unique natural products 
      from marine sponges, crinoids, and algae have been identified as HIF-1 activation 
      inhibitors. The US National Cancer Institute's Open Repository of marine 
      invertebrate and algae extracts has proven to be a valuable source of natural 
      product HIF-1 inhibitors. Among the active compounds identified, certain marine 
      natural products have also been shown to suppress the hypoxic induction of HIF-1 
      target genes such as vascular endothelial growth factor (VEGF). Some of these 
      marine HIF-1 inhibitors act by interfering with the generation of mitochondrial 
      signaling molecules in hypoxic cells. However, the precise mechanisms of action 
      for many newly identified marine natural product HIF-1 inhibitors remain 
      unresolved.
FAU - Nagle, Dale G
AU  - Nagle DG
AD  - Department of Pharmacognosy and Research Institute of Pharmaceutical Sciences, 
      School of Pharmacy, University of Mississippi, University, MS 38677-1848, USA.
FAU - Zhou, Yu-Dong
AU  - Zhou YD
LA  - eng
GR  - R01 CA098787/CA/NCI NIH HHS/United States
GR  - R01 CA098787-05A2/CA/NCI NIH HHS/United States
GR  - R56 CA098787/CA/NCI NIH HHS/United States
GR  - R56 CA098787-05A1/CA/NCI NIH HHS/United States
PT  - Journal Article
PL  - Netherlands
TA  - Phytochem Rev
JT  - Phytochemistry reviews : proceedings of the Phytochemical Society of Europe
JID - 101198162
PMC - PMC2901131
MID - NIHMS197011
EDAT- 2010/07/14 06:00
MHDA- 2010/07/14 06:01
PMCR- 2010/07/09
CRDT- 2010/07/13 06:00
PHST- 2010/07/13 06:00 [entrez]
PHST- 2010/07/14 06:00 [pubmed]
PHST- 2010/07/14 06:01 [medline]
PHST- 2010/07/09 00:00 [pmc-release]
AID - 10.1007/s11101-009-9120-1 [doi]
PST - ppublish
SO  - Phytochem Rev. 2009 Jun;8(2):415-429. doi: 10.1007/s11101-009-9120-1.