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

被引:40
作者
Aceves, Carmen [1 ]
Garcia-Solis, Pablo [1 ]
Arroyo-Helguera, Omar [1 ]
Vega-Riveroll, Laura [1 ]
Delgado, Guadalupe [1 ]
Anguiano, Brenda [1 ]
机构
[1] Univ Nacl Autonoma Mexico, Inst Neurobiol, Queretaro 76230, Mexico
基金
芬兰科学院;
关键词
BREAST-CANCER; PLASMINOGEN-ACTIVATOR; MOLECULAR-IODINE; ARACHIDONIC-ACID; GROWTH; IDENTIFICATION; EXPRESSION; APOPTOSIS; MARKERS; GOITER;
D O I
10.1186/1476-4598-8-33
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Introduction: Studies in mammary cancer demonstrated that moderately high concentrations of molecular iodine (I-2) 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 I-2 where analyzed. Results: I-2-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 cm(3)) 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 I-2 treatment. Tumors from I-2-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 (PPAR alpha). 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 (PPAR gamma). Conclusion: Together, these data demonstrate that the antineoplasic effect of iodine involves 6-IL formation and PPAR gamma induction.
引用
收藏
页数:9
相关论文
共 34 条
[1]   Is iodine a gatekeeper of the integrity of the mammary gland? [J].
Aceves, C ;
Anguiano, B ;
Delgado, G .
JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA, 2005, 10 (02) :189-196
[2]   Uptake and gene expression with antitumoral doses of iodine in thyroid and mammary gland:: Evidence that chronic administration has no harmful effects [J].
Anguiano, Brenda ;
Garcia-Solis, Pablo ;
Delgado, Guadalupe ;
Velasco, Carmen Aceves .
THYROID, 2007, 17 (09) :851-859
[3]   Prolactins are natural inhibitors of angiogenesis in the retina [J].
Aranda, J ;
Rivera, JC ;
Jeziorski, MC ;
Riesgo-Escovar, J ;
Nava, G ;
López-Barrera, F ;
Quiróz-Mercado, H ;
Berger, P ;
de la Escalera, GM ;
Clapp, C .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2005, 46 (08) :2947-2953
[4]   Uptake and anti proliferative effect of molecular iodine in the MCF-7 breast cancer cell line [J].
Arroyo-Helguera, O. ;
Anguiano, B. ;
Delgado, G. ;
Aceves, C. .
ENDOCRINE-RELATED CANCER, 2006, 13 (04) :1147-1158
[5]   Signaling pathways involved in the antiproliferative effect of molecular iodine in normal and tumoral breast cells: evidence that 6-iodolactone mediates apoptotic effects [J].
Arroyo-Helguera, O. ;
Rojas, E. ;
Delgado, G. ;
Aceves, C. .
ENDOCRINE-RELATED CANCER, 2008, 15 (04) :1003-1011
[6]   The mechanisms of action of PPARs [J].
Berger, J ;
Moller, DE .
ANNUAL REVIEW OF MEDICINE, 2002, 53 :409-435
[7]   Peroxisome Proliferator-Activated Receptor Alpha Is Crucial for Iloprost-Induced in vivo Angiogenesis and Vascular Endothelial Growth Factor Upregulation [J].
Biscetti, Federico ;
Gaetani, Eleonora ;
Flex, Andrea ;
Straface, Giuseppe ;
Pecorini, Giovanni ;
Angelini, Flavia ;
Stigliano, Egidio ;
Aprahamian, Tamar ;
Smith, Roy C. ;
Castellot, John J. ;
Pola, Roberto .
JOURNAL OF VASCULAR RESEARCH, 2009, 46 (02) :103-108
[8]   Hypothesis: Iodine, selenium and the development of breast cancer [J].
Cann, SA ;
van Netten, JP ;
van Netten, C .
CANCER CAUSES & CONTROL, 2000, 11 (02) :121-127
[9]   Predictive markers in breast and other cancers: A review [J].
Duffy, MJ .
CLINICAL CHEMISTRY, 2005, 51 (03) :494-503
[10]  
Duffy MJ, 2002, CLIN CHEM, V48, P1194