PMID- 17550131
OWN - NLM
STAT- MEDLINE
DCOM- 20070628
LR  - 20131121
IS  - 0392-9078 (Print)
IS  - 0392-9078 (Linking)
VI  - 26
IP  - 1
DP  - 2007 Mar
TI  - Cellular redox status regulates hypoxia inducible factor-1 activity. Role in 
      tumour development.
PG  - 39-50
AB  - The transcription factor hypoxia-inducible factor-1 (HIF-1) regulates the 
      expression of more than 100 genes involved in cellular adaptation and survival 
      under hypoxic stress. Activation of HIF-1 is associated with numerous 
      physiological and pathological processes that include tumorigenesis, vascular 
      remodelling, inflammation, and hypoxia/ischemia-related tissue damage. 
      Experimental data support the concept that modulation of Reactive Oxygen Species 
      (ROS) levels have an important impact on the hypoxic response mediated by HIF-1 
      alpha. However, ROS generation, the exact kinetics and conditions of ROS 
      production and their specific relevance to HIF-l alpha activation are issue still 
      to be clarified. Clinical studies suggested that HIF-1 activation correlates 
      directly with advanced disease stages and treatment resistance among cancer 
      patients. Preclinical studies support the inhibition of HIF-1 as a major 
      molecular target for anti-tumour drug discovery. Considerable effort is underway 
      to identify therapeutically useful molecule HIF-1 inhibitors. Most of the 
      compounds discovered to inhibit HIF-1 are natural products or synthetic compounds 
      with structures that are based on natural product leads. Natural products have 
      also served a vital role as molecular probes to elucidate the pathways that 
      regulate HIF-1 activity. Many of the substances found to inhibit HIF-I are 
      non-druggable compounds that are too cytotoxic to serve as drug leads. The 
      application of high-throughput screening methods, complementary 
      molecular-targeted assays, and structurally diverse chemical libraries hold 
      promise for the discovery of therapeutically useful HIF-1 inhibitors.
FAU - Martinez-Sanchez, G
AU  - Martinez-Sanchez G
AD  - Centre for Research and Biological Evaluations, Institute of Pharmacy and Food 
      Science, University of Havana, Havana, Cuba. gregorioms@informed.sld.cu
FAU - Giuliani, A
AU  - Giuliani A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - J Exp Clin Cancer Res
JT  - Journal of experimental & clinical cancer research : CR
JID - 8308647
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Reactive Oxygen Species)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/pharmacology/therapeutic use
MH  - Cell Hypoxia
MH  - Cell Transformation, Neoplastic/drug effects/*metabolism
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/antagonists & inhibitors/chemistry/*metabolism
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Models, Molecular
MH  - Neoplasms/drug therapy/*metabolism/physiopathology
MH  - Oxidation-Reduction
MH  - *Oxidative Stress/drug effects
MH  - Oxygen/metabolism
MH  - Protein Conformation
MH  - Reactive Oxygen Species/metabolism
MH  - *Signal Transduction/drug effects
RF  - 82
EDAT- 2007/06/07 09:00
MHDA- 2007/06/29 09:00
CRDT- 2007/06/07 09:00
PHST- 2007/06/07 09:00 [pubmed]
PHST- 2007/06/29 09:00 [medline]
PHST- 2007/06/07 09:00 [entrez]
PST - ppublish
SO  - J Exp Clin Cancer Res. 2007 Mar;26(1):39-50.