Antineoplastic effect of iodine in mammary cancer: participation of 6-iodolactone (6-IL) and peroxisome proliferator-activated receptors (PPAR).
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.
Aceves
Carmen
C
Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus UNAM-Juriquilla, Querétaro, México. caracev@servidor.unam.mx
García-Solís
Pablo
P
Arroyo-Helguera
Omar
O
Vega-Riveroll
Laura
L
Delgado
Guadalupe
G
Anguiano
Brenda
B
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
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