title: Antineoplastic effect of iodine in mammary cancer: participation of 6-iodolactone (6-IL) and peroxisome proliferator-activated receptors (PPAR).
abstract: BACKGROUND
  Studies in mammary cancer demonstrated that moderately high concentrations of molecular iodine (I2) have a antiproliferative and apoptotic effect either in vivo as in vitro, however the cellular intermediated involved in these effects has not been elucidated.
  
  
  METHODS
  Virgin Sprague-Dawley rats were treated with methyl-nitrosourea (MNU: single dose ip, 50 mg/Kg bw) and the participation of arachidonic acid (AA) and PPAR receptors in the antineoplasic effect of I2 where analyzed.
  
  
  RESULTS
  I2-treated rats for four weeks exhibited a significant reduction in the incidence (62.5 vs. 100%) and size (0.87 +/- 0.98 vs 1.96 +/- 1.5 cm3) of mammary tumors. HPLC analysis showed that tumoral but not normal mammary tissue contained an elevated basal concentration of AA and significantly more AA-iodinated called 6-iodolactone (6-IL) after chronic I2 treatment. Tumors from I2-treated rats showed fewer cells positive to proliferating cell nuclear antigen, lower blood vessel density, as well as decreases in vascular endothelial growth factor, urokinase-type plasminogen activator, and PPAR type alpha (PPARalpha). These same tumors showed increases in the cell death markers, TUNEL-positive cells (p < 0.05) and the enzyme caspase-3 (trend), as well as significant induction of PPAR type gamma (PPARgamma).
  
  
  CONCLUSIONS
  Together, these data demonstrate that the antineoplasic effect of iodine involves 6-IL formation and PPARgamma induction.
authors.affiliation: Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus UNAM-Juriquilla, Querétaro, México. caracev@servidor.unam.mx
authors.forename: Carmen
authors.initials: C
authors.lastname: Aceves
authors.forename: Pablo
authors.initials: P
authors.lastname: García-Solís
authors.forename: Omar
authors.initials: O
authors.lastname: Arroyo-Helguera
authors.forename: Laura
authors.initials: L
authors.lastname: Vega-Riveroll
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Delgado
authors.forename: Brenda
authors.initials: B
authors.lastname: Anguiano
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016718:Arachidonic Acid / Q000378:metabolism; D001095:Arachidonic Acids / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005260:Female; D007150:Immunohistochemistry; D007455:Iodine / Q000008:administration & dosage / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C026915:6-iodo-5-hydroxy-eicosatrienoic acid, delta-lactone; D000970:Antineoplastic Agents; D001095:Arachidonic Acids; D047492:Peroxisome Proliferator-Activated Receptors; D042461:Vascular Endothelial Growth Factor A; D016718:Arachidonic Acid; D007455:Iodine; D014568:Urokinase-Type Plasminogen Activator; D053148:Caspase 3