ABSTRACT
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.
Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Agents/pharmacology , Arachidonic Acids/pharmacology , Iodine/pharmacology , Prostate/drug effects , Prostatic Neoplasms/drug therapy , Adenocarcinoma/metabolism , Adenocarcinoma/secondary , Animals , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Gene Expression , Humans , Iodine/metabolism , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Prostate/metabolism , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathologyABSTRACT
The causes of late-Holocene centennial to millennial scale climatic variability and the impact that such variability had on tropical ecosystems are still poorly understood. Here, we present a high-resolution, multiproxy record from lowland eastern Mesoamerica, studied to reconstruct climate and vegetation history during the last 2,000 years, in particular to evaluate the response of tropical vegetation to the cooling event of the Little Ice Age (LIA). Our data provide evidence that the densest tropical forest cover and the deepest lake of the last two millennia were coeval with the LIA, with two deep lake phases that follow the Spörer and Maunder minima in solar activity. The high tropical pollen accumulation rates limit LIA's winter cooling to a maximum of 2 degrees C. Tropical vegetation expansion during the LIA is best explained by a reduction in the extent of the dry season as a consequence of increased meridional flow leading to higher winter precipitation. These results highlight the importance of seasonal responses to climatic variability, a factor that could be of relevance when evaluating the impact of recent climate change.