title: Uptake and efflux of rhenium in cells exposed to rhenium diseleno-ether and tissue distribution of rhenium and selenium after rhenium diseleno-ether treatment in mice.
abstract: We proposed a new water-soluble rhenium diseleno-ether compound (with one atom of Re and two atoms of Se) and investigated the uptake of Re into the nucleus of malignant cells in culture exposed to the compound for 48 h and its efflux from the nucleus after a post-exposure period of 48 h, as DNA is the main target of Re. We also studied the distribution of both Re and Se in the main organs after an oral administration of 10 or 40 mg/kg Re diseleno-ether to mice for four weeks, five days-a-week.
  
  
  METHODS
  Re and Se concentrations were assayed by inductively coupled plasma mass spectrometry (ICP-MS). Statistical analysis was performed using the Wilcoxon signed-rank test, comparing two related groups.
  
  
  RESULTS
  We observed that Re was well incorporated into the nucleus of malignant cells in the most sensitive cells MCF-7, derived from human breast cancer, and that there was no efflux of Re. In contrast, in MCF-7 resistant cells (MCF-7 Mdr and MCF-7 R), A549 and HeLa cells, there was significant efflux of Re from the nucleus after the wash-out period. In mice, an important and dose-dependent uptake of both Re and Se was observed in the liver, with lower concentrations in kidneys. The lowest concentrations were observed in blood, lung, spleen and bones. There was a significant increase of Re concentrations in the blood, liver and kidney in mice treated with Re diseleno-ether at the dose of 40 mg/kg/24 h versus those treated at the dose of 10 mg/kg/24 h. There was a significant increase of Se concentrations in all tissues with the dose of Re diseleno-ether of 10 mg/kg/24 h versus controls, and a significant increase in the liver in mice treated with dose of Re diseleno-ether of 40 mg/kg/24h versus those treated with 10 mg/kg/24 h.
  
  
  CONCLUSIONS
  We are the first to demonstrate that a compound combining Re and Se in a single molecule, is able to deliver Re and Se to the organism via an oral route, for cancer treatment.
authors.affiliation: Société de Coordination de Recherches Thérapeutiques, 20220 Algajola, France. philippe.collery@gmail.com.
authors.forename: Philippe
authors.initials: P
authors.lastname: Collery
authors.forename: Gérard
authors.initials: G
authors.lastname: Bastian
authors.forename: François
authors.initials: F
authors.lastname: Santoni
authors.forename: Ahmed
authors.initials: A
authors.lastname: Mohsen
authors.forename: Ming
authors.initials: M
authors.lastname: Wei
authors.forename: Thomas
authors.initials: T
authors.lastname: Collery
authors.forename: Alain
authors.initials: A
authors.lastname: Tomas
authors.forename: Didier
authors.initials: D
authors.lastname: Desmaele
authors.forename: Jean
authors.initials: J
authors.lastname: D'Angelo
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004986:Ether / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D051379:Mice; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000378:metabolism; D012211:Rhenium / Q000737:chemistry / Q000378:metabolism*; D012643:Selenium / Q000737:chemistry / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D019275:Radiopharmaceuticals; D004986:Ether; D012211:Rhenium; D012643:Selenium
keywords: AKT; MTOR; NF-κB; PI3K; Rhenium; cancer; immune system; inflammation; rhenium diseleno-ether compound; selenium; tissue distribution