PMID- 20089365
OWN - NLM
STAT- MEDLINE
DCOM- 20100818
LR  - 20211203
IS  - 1532-2777 (Electronic)
IS  - 0306-9877 (Linking)
VI  - 74
IP  - 5
DP  - 2010 May
TI  - Practical strategies for suppressing hypoxia-inducible factor activity in cancer 
      therapy.
PG  - 789-97
LID - 10.1016/j.mehy.2009.12.022 [doi]
AB  - The utility of anti-angiogenic strategies for cancer control is strongly 
      compromised by hypoxia-driven phenotypic changes in cancer cells, which make 
      cancer cells more invasive and more prone to give rise to metastases. A key 
      mediator of this phenotypic shift is the transcription factor hypoxia-inducible 
      factor-1 (HIF-1), which acts directly and indirectly to promote the 
      epidermal-mesenchymal transition, boost cancer invasiveness, increase production 
      of angiogenic factors, and induce chemoresistance. In some cancers, HIF-1 
      activity is constitutively elevated even in aerobic environments, making the 
      cancer harder to treat and control. Practical strategies for suppressing HIF-1 
      activation may include the following: inhibiting NF-kappaB activation with 
      salicylic acid and/or silibinin, which should decrease transcription of the 
      HIF-1alpha gene; suppressing translation of HIF-1alpha mRNA with drugs that 
      inhibit mTOR or topoisomerase I; supporting the effective activity of prolyl 
      hydroxylases - which promote proteasomal degradation of HIF-1alpha under aerobic 
      conditions - with antioxidant measures, alpha-ketoglutarate, and possibly 
      dichloroacetate; promoting the O(2)-independent proteasomal degradation of 
      HIF-1alpha with agents that inhibit the chaperone protein Hsp90; and blocking 
      HIF-1 binding to its DNA response elements with anthracyclines. The utility of 
      various combinations of these strategies should be tested in cancer cell cultures 
      and rodent xenograft models; initial efforts in this regard have yielded 
      encouraging results. Comprehensive strategies for suppressing HIF-1 activity can 
      be expected to complement the efficacy of cancer chemotherapy and of effective 
      anti-angiogenic regimens.
FAU - McCarty, Mark F
AU  - McCarty MF
AD  - Oasis of Hope Hospital, Paseo Playas 19, Playas de Tijuana, Tijuana, B.C., 
      Mexico. mccarty@pantox.com
FAU - Barroso-Aranda, Jorge
AU  - Barroso-Aranda J
FAU - Contreras, Francisco
AU  - Contreras F
LA  - eng
PT  - Journal Article
DEP - 20100120
PL  - United States
TA  - Med Hypotheses
JT  - Medical hypotheses
JID - 7505668
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Anthracyclines)
RN  - 0 (Cardiac Glycosides)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Silymarin)
RN  - 4RKY41TBTF (Silybin)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 5.99.1.2 (DNA Topoisomerases, Type I)
RN  - O414PZ4LPZ (Salicylic Acid)
SB  - IM
MH  - Angiogenesis Inhibitors/*adverse effects/therapeutic use
MH  - Anthracyclines/pharmacology
MH  - Cardiac Glycosides/pharmacology
MH  - Cell Hypoxia/physiology
MH  - DNA Topoisomerases, Type I/pharmacology
MH  - Gene Expression Regulation/*drug effects
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/*metabolism
MH  - Intracellular Signaling Peptides and Proteins/metabolism
MH  - NF-kappa B/antagonists & inhibitors
MH  - Neoplasm Invasiveness/*prevention & control
MH  - Neoplasms/*drug therapy
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Salicylic Acid/pharmacology
MH  - Silybin
MH  - Silymarin/pharmacology
MH  - TOR Serine-Threonine Kinases
EDAT- 2010/01/22 06:00
MHDA- 2010/08/19 06:00
CRDT- 2010/01/22 06:00
PHST- 2009/12/11 00:00 [received]
PHST- 2009/12/16 00:00 [accepted]
PHST- 2010/01/22 06:00 [entrez]
PHST- 2010/01/22 06:00 [pubmed]
PHST- 2010/08/19 06:00 [medline]
AID - S0306-9877(09)00834-2 [pii]
AID - 10.1016/j.mehy.2009.12.022 [doi]
PST - ppublish
SO  - Med Hypotheses. 2010 May;74(5):789-97. doi: 10.1016/j.mehy.2009.12.022. Epub 2010 
      Jan 20.