Abstract B40: Uptake and potential antineoplasic effects of iodine on prostate cancer in the TRAMP model
Authors: Olvera Paloma , Delgado Guadalupe , Aceves Carmen , Anguiano Brenda 
Published: May 2013

Prostate cancer is the second most frequently diagnosed cancer in men worldwide, but incidence rates vary, being lower in Japan than in the USA. This low incidence in Japanese populations has been explained by the high intake of iodine (5280 μg/day in Japan vs 209 μg in USA), among other factors. Studies in thyroid and breast cancer have shown that iodine supplementation induces apoptosis, reduces cell proliferation, and decreases the expression of cell invasion factors (VEGF, uPa, uPAR). In both tissues, iodide (I−) uptake is mediated by the Na+/I− symporter (NIS), whereas iodine (I2) uptake depends on a facilitated diffusion mechanism. Our group showed that I− or I2 supplementation of rats with prostate hyperplasia (induced with sex hormones) decreases the DNA content and has no harmful effect on normal tissue. In human prostate cancer cells (LNCaP), I− uptake is mediated via NIS, while I2 uptake is independent from NIS. Both I− and I2 treatment activated the apoptotic pathway mediated by Bax/Bcl2, and caspases, suggesting that either form of iodine might be used as an antineoplastic agent against prostate cancer. Here, we determined the uptake of I− and I2 in normal (WT) and tumoral mouse prostate, and analyzed the effect of a mixed iodide/iodine (0.5 mg I−+ 0.25 mg I2) supplement (starting at 6 weeks of age) on the progression of prostate cancer in a transgenic model (Transgenic Adenocarcinoma of Mouse Prostate, TRAMP). The TRAMP mice developed intraepithelial neoplastic lesions (PIN) and cancer around 12 and 24 weeks of age, respectively. Iodine uptake was analyzed with radioactive tracers (125I− and 125I2), which were ip injected into WT and TRAMP mice at these two ages. The radiolabel was quantified at 120 min post-injection in a gamma counter. The results showed that normal and tumoral prostates take up both chemical forms of iodine, but only I− uptake is blocked by the classic NIS inhibitor perchlorate. These data corroborate NIS participation in I− uptake and support the notion that another transporter mediates I2 uptake. Iodine supplementation had no effect on the genitourinary tract weight, histopathological acini aspect (hematoxylin-eosina stain), or proliferative rate (immunoreactivity to proliferating cell nuclear antigen) of any groups. Currently, we are analyzing the effect of iodine on tumor apoptosis and the expression of molecular factors associated with cell invasion and metastasis (epithelial-mesenchymal transition).

The authors are grateful to Felipe Ortiz and Martín García for their technical assistance. Supported by CONACYT (78955, 87196, 127368), PAPIIT (IN201210).

Citation Format: Paloma Olvera, Guadalupe Delgado, Carmen Aceves, Brenda Anguiano. Uptake and potential antineoplasic effects of iodine on prostate cancer in the TRAMP model [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr B40.