A complex between 6-iodolactone and the peroxisome proliferator-activated receptor type gamma may mediate the antineoplastic effect of iodine in mammary cancer.
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.
Nuñez-Anita
R E
RE
Instituto de Neurobiología, Universidad Nacional Autónoma de México, Juriquilla Querétaro, Mexico.
Arroyo-Helguera
O
O
Cajero-Juárez
M
M
López-Bojorquez
L
L
Aceves
C
C
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
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