Abstract
Iodine supplementation exerts antitumor effects in several types of cancer. Iodide (I⁻) and iodine (I₂) reduce cell proliferation and induce apoptosis in human prostate cancer cells (LNCaP and DU-145). Both chemical species decrease tumor growth in athymic mice xenografted with DU-145 cells. The aim of this study was to analyze the uptake and effects of iodine in a preclinical model of prostate cancer (transgenic adenocarcinoma of the mouse prostate [TRAMP] mice/SV40-TAG antigens), which develops cancer by 12 wks of age. ¹²⁵I⁻ and ¹²⁵I₂ uptake was analyzed in prostates from wild-type and TRAMP mice of 12 and 24 wks in the presence of perchlorate (inhibitor of the Na⁺/I⁻ symporter [NIS]). NIS expression was quantified by quantitative polymerase chain reaction (qPCR). Mice (6 wks old) were supplemented with 0.125 mg I⁻ plus 0.062 mg I₂/mouse/day for 12 or 24 wks. The weight of the genitourinary tract (GUT), the number of acini with lesions, cell proliferation (levels of proliferating cell nuclear antigen [PCNA] by immunohistochemistry), p53 and p21 expression (by qPCR) and apoptosis (relative amount of nucleosomes by enzyme-linked immunosorbent assay) were evaluated. In both age-groups, normal and tumoral prostates take up both forms of iodine, but only I⁻ uptake was blocked by perchlorate. Iodine supplementation prevented the overexpression of NIS in the TRAMP mice, but had no effect on the GUT weight, cell phenotype, proliferation or apoptosis. In TRAMP mice, iodine increased p53 expression but had no effect on p21 (a p53-dependent gene). Our data corroborate NIS involvement in I⁻ uptake and support the notion that another transporter mediates I₂ uptake. Iodine did not prevent cancer progression. This result could be explained by a strong inactivation of the p53 pathway by TAG antigens.
Highlights
Prostate cancer is the second most frequently diagnosed cancer in men worldwide, with an incidence significantly lower in Japan than in the United States (22.7 versus 83.8/100,000 per year, respectively) [1]
Japan is 25-fold higher than in Western countries (5,280 μg in Japan versus 209 μg in the US) [3,4]. This chemoprotection by iodine is evident in thyroid and breast cancer, and it seems to be related to the ability of these tissues to take up and metabolize iodide (I–) and/or molecular iodine (I2) [5]
TRAMP mice exhibited high Na+/I– symporter (NIS) expression compared to wild-type mice
Summary
Prostate cancer is the second most frequently diagnosed cancer in men worldwide, with an incidence significantly lower in Japan than in the United States (22.7 versus 83.8/100,000 per year, respectively) [1]. This lower risk has been associated with lifestyle factors such as diet. Japan is 25-fold higher than in Western countries (5,280 μg in Japan versus 209 μg in the US) [3,4] This chemoprotection by iodine is evident in thyroid and breast cancer, and it seems to be related to the ability of these tissues to take up and metabolize iodide (I–) and/or molecular iodine (I2) [5]. For I– to exert some of these effects, it must be converted to an oxidized species of iodine by specific peroxidases (thyro-, lacto- or myeloperoxidase) [15,16,17]
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