title: A complex between 6-iodolactone and the peroxisome proliferator-activated receptor type gamma may mediate the antineoplastic effect of iodine in mammary cancer.
abstract: Recently we and other groups have shown that molecular iodine (I(2)) exhibits potent antiproliferative 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.
authors.affiliation: Instituto de Neurobiología, Universidad Nacional Autónoma de México, Juriquilla Querétaro, Mexico.
authors.forename: R E
authors.initials: RE
authors.lastname: Nuñez-Anita
authors.forename: O
authors.initials: O
authors.lastname: Arroyo-Helguera
authors.forename: M
authors.initials: M
authors.lastname: Cajero-Juárez
authors.forename: L
authors.initials: L
authors.lastname: López-Bojorquez
authors.forename: C
authors.initials: C
authors.lastname: Aceves
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016718:Arachidonic Acid / Q000032:analysis / Q000737:chemistry; D001095:Arachidonic Acids / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D019295:Computational Biology; D024202:Electrophoretic Mobility Shift Assay; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007455:Iodine / Q000494:pharmacology* / Q000627:therapeutic use; D007457:Iodine Radioisotopes / Q000737:chemistry; D047493:PPAR alpha / Q000378:metabolism; D047495:PPAR gamma / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D020218:Response Elements; D047488:Retinoid X Receptors / Q000737:chemistry / Q000378:metabolism; D013194:Staining and Labeling
chemical_list: C026915:6-iodo-5-hydroxy-eicosatrienoic acid, delta-lactone; D000970:Antineoplastic Agents; D001095:Arachidonic Acids; D007457:Iodine Radioisotopes; D047493:PPAR alpha; D047495:PPAR gamma; D047488:Retinoid X Receptors; D016718:Arachidonic Acid; D007455:Iodine