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Int. J. Mol. Sci. 2016, 17(6), 903; doi:10.3390/ijms17060903

The Effect of Analogues of 1α,25-Dihydroxyvitamin D2 on the Regrowth and Gene Expression of Human Colon Cancer Cells Refractory to 5-Fluorouracil

1
Department of Immunology, Maria Skłodowska-Curie Memorial Cancer Centre and Institute of Oncology, 5 WK Roentgen, 02-781 Warsaw, Poland
2
Chemistry Department, Pharmaceutical Research Institute, 8 Rydygiera, 01-793 Warsaw, Poland
3
Pharmacology Department, Pharmaceutical Research Institute, 8 Rydygiera, 01-793 Warsaw, Poland
These authors equally contributed to this study.
*
Author to whom correspondence should be addressed.
Academic Editor: Roman Perez-Fernandez
Received: 10 May 2016 / Revised: 31 May 2016 / Accepted: 1 June 2016 / Published: 14 June 2016
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Abstract

This study aimed to evaluate the capacity of hypocalcemic analogues of 1α,25-dihydroxyvitamin D2 (1,25D2) and 1α,25-dihydroxyvitamin D3 (1,25D3) to inhibit regrowth and regulate the stemness-related gene expression in colon cancer cells undergoing renewal after exposure to 5-fluorouracil (5-FU). All of the tested analogues of 1,25D2 equally potently decreased the clonogenicity and the proliferative activity of HT-29 cells which survived the exposure to 5-FU, but differently regulated gene expression of these cells during their renewal. 1,25D2 and analogues (PRI-1907 and PRI-1917), as well as 1,25D3 and analogue PRI-2191, decreased the relative expression level of several stemness-related genes, such as NANOG, OCT3/4, PROM1, SOX2, ALDHA1, CXCR4, in HT-29/5-FU cells during their renewal, in comparison to untreated HT-29/5-FU cells. The other 1,25D2 analogues (PRI-1906 and PRI-1916) were not capable of downregulating the expression of these stemness-related genes as the analogues PRI-1907 and PRI-1917 did. All of the tested vitamin D analogues upregulated CDH1, the gene encoding E-cadherin associated with epithelial phenotype. Out of the series of analogues studied, side-chain branched analogues of 1,25D2 (PRI-1907, PRI-1917) and the analogue of 1,25D3 (PRI-2191) might be used to target cancer cells with stem-like phenotypes that survive conventional chemotherapy. View Full-Text
Keywords: 1α,25-dihydroxyvitamin D2; 1α,25-dihydroxyvitamin D3; vitamin D analogues; vitamin D and chemotherapy; cancer and vitamin D; cancer stem cell; colorectal cancer; HT-29 cell line 1α,25-dihydroxyvitamin D2; 1α,25-dihydroxyvitamin D3; vitamin D analogues; vitamin D and chemotherapy; cancer and vitamin D; cancer stem cell; colorectal cancer; HT-29 cell line
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Neska, J.; Swoboda, P.; Przybyszewska, M.; Kotlarz, A.; Bolla, N.R.; Miłoszewska, J.; Grygorowicz, M.A.; Kutner, A.; Markowicz, S. The Effect of Analogues of 1α,25-Dihydroxyvitamin D2 on the Regrowth and Gene Expression of Human Colon Cancer Cells Refractory to 5-Fluorouracil. Int. J. Mol. Sci. 2016, 17, 903.

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