title: Curcumin decreases survival of Hep3B liver and MCF-7 breast cancer cells: the role of HIF.
abstract: BACKGROUND
  Curcumin, a commonly used spice, affects the activities of cytokines, enzymes, and transcription factors that are linked to inflammation. Furthermore, curcumin has been assigned tumor growth inhibiting effects, possibly mediated by promoting hypoxia-inducible factor (HIF) degradation. HIFs are transcription factors that play a central role in the adaptation and response to low oxygen levels in metazoan cells. However, curcumin also exhibits properties of an iron chelator indicating its potential of inhibiting HIF-α prolyl hydroxylase (PHD) activity.
  
  
  METHODS
  We were interested in clarifying these divergent actions of curcumin in due consideration of the effects on radio-therapy. Thus, concentration- and time-dependent effects of curcumin on HIF-α and -β protein levels and activity in hepatoma and breast carcinoma cell cultures under normoxic and hypoxic conditions were studied.
  
  
  RESULTS
  It was shown that HIF-1α accumulated in normoxia after the application of higher doses of the drug. Curcumin proved to lower HIF-1α and HIF-2α protein levels in hypoxia. HIF-1β (ARNT; arylhydrocarbon nuclear translocator) protein levels and HIF transcriptional activity were reduced in normoxia and hypoxia after 4 h and 24 h incubation periods. Furthermore, curcumin treatment negatively impacted on clonogenic cell survival of Hep3B hepatoma and MCF-7 breast carcinoma cells.
  
  
  CONCLUSIONS
  Effects of curcumin on cell growth and survival factor expression suggest its potential benefit in the treatment of cancer without a direct radiosensitizing influence of curcumin on these cells.
authors.affiliation: Department of Physiology, Center for Structural and Cell Biology in Medicine, University of Luebeck, Luebeck, Germany. troefer@physio.uni-luebeck.de
authors.forename: Mareike
authors.initials: M
authors.lastname: Ströfer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Jelkmann
authors.forename: Reinhard
authors.initials: R
authors.lastname: Depping
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects* / Q000528:radiation effects; D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D028527:Cuminum; D004305:Dose-Response Relationship, Drug; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D008517:Phytotherapy; D028321:Plant Preparations / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014410:Tumor Stem Cell Assay; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D028321:Plant Preparations; D011838:Radiation-Sensitizing Agents; D000099162:Endothelial PAS Domain-Containing Protein 1; C497396:ARNT protein, human; C497442:HIF1A protein, human