Antineoplastic effect of iodine in mammary cancer: participation of 6-iodolactone (6-IL) and peroxisome proliferator-activated receptors (PPAR).

Author(s): Aceves C, Garcia-Solis P, Arroyo-Helguera O, Vega-Riveroll L, Delgado G, Anguiano B

Affiliation(s): Instituto de Neurobiologia, Universidad Nacional Autonoma de Mexico, Campus UNAM-Juriquilla, Queretaro, Mexico. caracev@servidor.unam.mx

Publication date & source: 2009-06-06, Mol Cancer., 8:33.

Publication type: Research Support, Non-U.S. Gov't

INTRODUCTION: 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). CONCLUSION: Together, these data demonstrate that the antineoplasic effect of iodine involves 6-IL formation and PPARgamma induction.