title: ANTIPROLIFERATIVE AND CYTOTOXIC EFFECT OF SELECTED VITAMIN D ANALOGS ON NASAL POLYPS FIBROBLASTS AND OTHER CELLS WITH HIGHER PROLIFERATIVE POTENTIAL.
abstract: Besides well-known effect on bone and mineral metabolism vitamin D is involved in essential non-calcemic regulatory mechanisms, such as cellular proliferation, differentiation and apoptosis in various cell types. Major limitation for therapeutic use of calcitriol, a hormonally active form of vitamin D, is its calcemic and phosphatemic action. Recently, more selective vitamin D analogs which retain clinically useful activities with reduced toxicity have been designed. The aim of the present study was to evaluate the in vitro effect of vitamin D analogs on proliferation rate and survivability of cells with increased proliferative activity. The effect of calcitriol, PRI-2191, PRI-1890, PRI-1906 and PRI-2205 was examined. The experiments were performed on cultures derived from nasal polyps and cancer cells lines (SNB-19, C32 and SH-4). Cultures were incubated 72 h with tested compounds, each at the concentration of 0.025, 0.25, 2.5 and 25 µg/mL. The cytotoxic effect of vitamin D analogs and their influence on growth rate were determined using WST-1 assay. RT-QPCR technique was used to evaluate the expression of anti-apoptotic BCL-2 and pro-apoptotic BAX gene. Each of the tested compounds presented significant effect at the concentrations above 0.25 µg/mL. The strongest inhibition of the growth rate and decrease in cell survivability was observed after treatment with PRI-1890 and PRI-2191. Stimulation with calcitriol and other vitamin D analogs led to decrease BCL-2/BAX mRNA ratio in each cell lines. The apparent pro-apoptotic action revealed PRI-2191 followed by PRI-1890. It might be hypothesized that vitamin D analogs supplementation may provide therapeutic benefits not only in oncological patients but also in chronic rhinosinusitis.
authors.forename: Marcin
authors.initials: M
authors.lastname: Frączek
authors.forename: Dariusz
authors.initials: D
authors.lastname: Kuśmierz
authors.forename: Beata
authors.initials: B
authors.lastname: Rostkowska-Nadolska
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kutner
authors.forename: Małgorzata T
authors.initials: MT
authors.lastname: Latocha
mesh_terms: D002117:Calcitriol / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects; D019254:Genes, bcl-2; D006801:Humans; D009298:Nasal Polyps / Q000188:drug therapy* / Q000473:pathology; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: C494826:BAX protein, human; D051028:bcl-2-Associated X Protein; D014807:Vitamin D; D002117:Calcitriol