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Antiproliferative and cytotoxic effect of vitamin D3 and its derivatives on the selected cells with a higher proliferative potential

Marcin Frączek 1Dariusz Kuśmierz 2Beata Rostkowska-Nadolska 1Andrzej Kutner 3Małgorzata T. Latocha 2

1. Wroclaw Medical University, Dept. of Otolaryngology (WMU), Borowska 213, Wrocław 50-556, Poland
2. Department of Cell Biology, Medical University of Silesia (SUM), Jedności 8, Sosnowiec 41-200, Poland
3. Pharmaceutical Research Institute (IF), Rydygiera 8, Warszawa 01-793, Poland


There are many reports in the literature on multidirectional activity of vitamin D and its analogs. Recently, the role of vitamin D derivates as potential anti-proliferative agents in addition to the well-known application in the treatment of rickets and osteoporosis has been revealed. Studies on the mechanisms of action of vitamin D and its analogs demonstrated that calcitriol, hormonally active form of vitamin D, has a regulatory effect toward cells’ proliferation, division and differentiation. Numerous researches revealed also the influence of those substances on apoptosis and inhibition of cell proliferation in certain types of malignant tumors.
The aim of the present study was to evaluate the in vitro effect of new derivatives of vitamin D3 on the divisions and viability of the cells with increased proliferative activity. The effect of calcitriol, tacalcitol and three new derivatives of vitamin D3 synthesized at the Pharmaceutical Research Institute in Warsaw, coded as PRI-1890, PRI-1906 and PRI-2205 was examined.
All the tests were performed on tumor cell lines (SNB-19, C-32 and SH-4), cultures derived from nasal polyp tissues and cultures of normal skin fibroblasts (HFF-1). Cultures were set and carried out in 75ml Nunc cell culture vessel, then the cells were seeded into 96-well plates and after 24h incubation calcitriol, tacalcitol, RPI-1890, RPI-1906 and RPI-2205 at a concentration of 0.025, 0.25, 2.5 and 25ug/ml were added to the medium. After subsequent 72h the number of cells was determined in cultures using the WST-1 assay (Roche Molecular Biochemicals). We analyzed both the survival and proliferative activity of cells treated with the above derivatives of vitamin D3. RT-QPCR technique was used to determine the expression of anti-apoptotic Bcl -2 gene and pro-apoptotic BAX gene.

Tested compounds show the most significant effects at the concentrations above 0.25ug/ml. Calcitriol had the smallest impact on both the proliferation and cell viability. Contrary, the strongest inhibition of the proliferation and decrease in cell viability was observed after the use of vitamin D analog  PRI-1890.

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Submitted: 2014-03-15 09:06
Revised:   2014-04-28 18:58