A complex between 6-iodolactone and the peroxisome proliferator-activated receptor type gamma may mediate the antineoplasic effect of iodine in mammary cancer

Recently we and other groups have shown that molecular iodine (I-2) exhibits potent anti proliferative and apoptotic effects in mammary cancer models. In the human breast cancer cell line MCF-7, I-2 treatment generates iodine-containing lipids similar to 6-iodo-5-hydroxy-eicosatrienoic acid and the 6-iodolactone (6-IL) derivative of arachidonic acid (AA), and it significantly decreases cellular proliferation and induces caspase-dependent apoptosis. Several studies have shown that AA is a natural ligand of the peroxisome proliferator-activated receptors (PPARs), which are nuclear transcription factors thought to participate in regulating cancer cell proliferation. Our results show that in MCF-7 cells: (1) 6-IL binds specifically and with high affinity to PPAR proteins (EMSA assays), (2) 6-IL activates both transfected (by transactivation assays) and endogenous (by lipid accumulation) peroxisome proliferator response elements, and (3) 6-IL supplementation increases PPAR gamma and decreases PPAR alpha expression. These results implicate PPARs in a molecular mechanism by which I-2, through formation of 6-IL, inhibits the growth of human breast cancer cells. (C) 2009 Elsevier Inc. All rights reserved.