Uptake and antitumoral effects of iodine and 6-iodolactone in differentiated and undifferentiated human prostate cancer cell lines.

BACKGROUND: Evidence indicates that iodine per se could be implicated in the physiology of several organs that can internalize it. In thyroid and breast cancer, iodine treatments inhibit cell proliferation and induce apoptosis through a direct (mitochondria) and/or indirect effect (iodolipid generation). Here, we determined the uptake of iodide (I(-) ) and iodine (I(2) ), as well as the antiproliferative and apoptotic effects of 6-iodolactone (6-IL) and both forms of iodine in human prostate cells lines. METHODS: Non-cancerous (RWPE-1) and cancerous (LNCaP, DU-145) cells, as well as nude mice xenotransplanted with DU-145 cells were used as cancer models. Iodine uptake was analyzed with radioactive tracers, transporter expression by qRT-PCR, cell proliferation by blue trypan, apoptosis by enzyme immunoassay or fluorescence, BAX and BCL-2 by western-blot, and caspsase 3 by enzymatic assay. RESULTS: All three cell lines take up both forms of iodine. In RWPE-1 cells, I(-) uptake depends on the Na(+) /I(-) symporter (NIS), whereas it was independent of NIS in LNCaP and DU-145 cells. Antiproliferative effects of iodine and 6-IL were dose and time dependent; RWPE-1 was most sensitive to I(-) and 6-IL, whereas LNCaP was more sensitive to I(2) . In the three cell lines both forms of iodine activated the intrinsic apoptotic pathway (increasing the BAX/BCL-2 index and caspases). Iodine supplementation impaired growth of the DU-145 tumor in nude mice. CONCLUSION: Normal and cancerous prostate cells can take up iodine, and depending on the chemical form, it exerts antiproliferative and apoptotic effects both in vitro and in vivo.

Epididymis expresses the highest 5'-deiodinase activity in the male reproductive system: kinetic characterization, distribution, and hormonal regulation.

We characterized the enzymes that catalyze the deiodination of T(4) to T(3) in the male reproductive tract. Testis, epididymis (EPI), seminal vesicles, prostate, bulbourethral glands, spermatozoa, and semen were taken from sexually mature rats (300 g). Iodothyronine 5'-deiodinase (5'-D) activity was quantified by the radiolabeled-iodide-release method. 5'-D activity was 10-fold higher in EPI and semen than in the rest of the tissues. In EPI, semen, and prostate, the enzymatic activity was completely inhibited by 1 mm 6-n-propyl-2-thiouracil, whereas in the other tissues the inhibition was partial (50%). The high susceptibility to 6-n-propyl-2-thiouracil inhibition, a ping-pong kinetic pattern, and low cofactor (Michaelis Menten constant for dithiothreitol=0.7 mm) and high substrate (Michaelis Menten constant for reverse T(3)=0.4 microm) requirements indicate that EPI 5'-D corresponds to type 1 deiodinase (D1). Real-time RT-PCR amplification of D1 mRNA in this tissue confirms this conclusion. The highest EPI D1 expression occurred at the onset of puberty and sexual maturity, and in the adult, this activity was more abundant in corpus and caput than in the caudal region. EPI D1 expression was elevated under conditions of hyperthyroidism and with addition of 17beta-estradiol. Our data also showed a direct association between D1 and a functional epididymis marker, the neutral alpha-glucosidase enzyme, suggesting that local generation of T(3) could be associated with the development and function of EPI and/or spermatozoa maturation. Further studies are necessary to analyze the possible physiological relevance of 5'-D in the male reproductive system.