The Effect of Analogues of 1α,25-Dihydroxyvitamin D₂ on the Regrowth and Gene Expression of Human Colon Cancer Cells Refractory to 5-Fluorouracil.
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.
Department of Immunology, Maria Sk&#322;odowska-Curie Memorial Cancer Centre and Institute of Oncology, 5 WK Roentgen, 02-781 Warsaw, Poland. jacek.neska91@gmail.com.
Jacek
J
Neska
Department of Immunology, Maria Sk&#322;odowska-Curie Memorial Cancer Centre and Institute of Oncology, 5 WK Roentgen, 02-781 Warsaw, Poland. pswoboda@o2.pl.
Paweł
P
Swoboda
Department of Immunology, Maria Sk&#322;odowska-Curie Memorial Cancer Centre and Institute of Oncology, 5 WK Roentgen, 02-781 Warsaw, Poland. magip@coi.waw.pl.
Małgorzata
M
Przybyszewska
Department of Immunology, Maria Sk&#322;odowska-Curie Memorial Cancer Centre and Institute of Oncology, 5 WK Roentgen, 02-781 Warsaw, Poland. akotlarz@coi.waw.pl.
Agnieszka
A
Kotlarz
Chemistry Department, Pharmaceutical Research Institute, 8 Rydygiera, 01-793 Warsaw, Poland. n.bolla@ifarm.eu.
Narasimha Rao
NR
Bolla
Department of Immunology, Maria Sk&#322;odowska-Curie Memorial Cancer Centre and Institute of Oncology, 5 WK Roentgen, 02-781 Warsaw, Poland. joannam@coi.waw.pl.
Joanna
J
Miłoszewska
Department of Immunology, Maria Sk&#322;odowska-Curie Memorial Cancer Centre and Institute of Oncology, 5 WK Roentgen, 02-781 Warsaw, Poland. m.a.grygorowicz@gmail.com.
Monika Anna
MA
Grygorowicz
Pharmacology Department, Pharmaceutical Research Institute, 8 Rydygiera, 01-793 Warsaw, Poland. a.kutner@ifarm.eu.
Andrzej
A
Kutner
Department of Immunology, Maria Sk&#322;odowska-Curie Memorial Cancer Centre and Institute of Oncology, 5 WK Roentgen, 02-781 Warsaw, Poland. sergiusz.markowicz@coi.pl.
Sergiusz
S
Markowicz
D000970:Antineoplastic Agents / Q000633:toxicity; D002117:Calcitriol / Q000031:analogs & derivatives / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000633:toxicity; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D014815:Vitamins / Q000494:pharmacology*
D000970:Antineoplastic Agents; D014815:Vitamins; D002117:Calcitriol; D005472:Fluorouracil
1α,25-dihydroxyvitamin D2; 1α,25-dihydroxyvitamin D3; HT-29 cell line; cancer and vitamin D; cancer stem cell; colorectal cancer; vitamin D analogues; vitamin D and chemotherapy