Next Article in Journal
The Systemic Profile of Soluble Immune Mediators in Patients with Myelodysplastic Syndromes
Next Article in Special Issue
1α,25(OH)2D3 Suppresses the Migration of Ovarian Cancer SKOV-3 Cells through the Inhibition of Epithelial–Mesenchymal Transition
Previous Article in Journal
Protonation Sites, Tandem Mass Spectrometry and Computational Calculations of o-Carbonyl Carbazolequinone Derivatives
Previous Article in Special Issue
The Effect of Analogues of 1α,25-Dihydroxyvitamin D2 on the Regrowth and Gene Expression of Human Colon Cancer Cells Refractory to 5-Fluorouracil
Article

Prodifferentiation Activity of Novel Vitamin D2 Analogs PRI-1916 and PRI-1917 and Their Combinations with a Plant Polyphenol in Acute Myeloid Leukemia Cells

1
Department of Clinical Biochemistry and Pharmacology, Ben Gurion University of the Negev, Beer Sheva 841051, Israel
2
Department of Chemistry and Department of Pharmacology, Pharmaceutical Research Institute, Warsaw 01-793, Poland
*
Author to whom correspondence should be addressed.
Academic Editor: Roman Perez-Fernandez
Int. J. Mol. Sci. 2016, 17(7), 1068; https://doi.org/10.3390/ijms17071068
Received: 11 May 2016 / Revised: 21 June 2016 / Accepted: 28 June 2016 / Published: 5 July 2016
1α,25-dihydroxyvitamin D3 (1,25D3) is a powerful differentiation inducer for acute myeloid leukemia (AML) cells. However, 1,25D3 doses required for differentiation of AML cells may cause lethal hypercalcemia in vivo. There is evidence that vitamin D2 is less toxic than vitamin D3 in animals. Here, we determined the differentiation effects of novel analogs of 1α,25-dihydroxyvitamin D2 (1,25D2), PRI-1916 and PRI-1917, in which the extended side chains of their previously reported precursors (PRI-1906 and PRI-1907, respectively) underwent further 24Z (24-cis) modification. Using four human AML cell lines representing different stages of myeloid maturation (KG-1a, HL60, U937, and MOLM-13), we found that the potency of PRI-1916 was slightly higher or equal to that of PRI-1906 while PRI-1917 was significantly less potent than PRI-1907. We also demonstrated that 1,25D2 was a less effective differentiation agent than 1,25D3 in these cell lines. Irrespective of their differentiation potency, all the vitamin D2 derivatives tested were less potent than 1,25D3 in transactivating the DR3-type vitamin D response elements. However, similar to 1,25D3, both 1,25D2 and its analogs could strongly cooperate with the plant polyphenol carnosic acid in inducing cell differentiation and inhibition of G1–S cell cycle transition. These results indicate that the 24Z modification has contrasting effects on the differentiation ability of PRI-1906 and PRI-1907 and that the addition of a plant polyphenol could result in a similar extent of cell differentiation induced by different vitamin D compounds. The enhanced antileukemic effects of the tested combinations may constitute the basis for the development of novel approaches for differentiation therapy of AML. View Full-Text
Keywords: acute myeloid leukemia; analogs of 1α,25-dihydroxyvitamin D2; vitamin D receptor; retinoid X receptor; carnosic acid; cell differentiation; cell cycle distribution acute myeloid leukemia; analogs of 1α,25-dihydroxyvitamin D2; vitamin D receptor; retinoid X receptor; carnosic acid; cell differentiation; cell cycle distribution
Show Figures

Graphical abstract

MDPI and ACS Style

Nachliely, M.; Sharony, E.; Bolla, N.R.; Kutner, A.; Danilenko, M. Prodifferentiation Activity of Novel Vitamin D2 Analogs PRI-1916 and PRI-1917 and Their Combinations with a Plant Polyphenol in Acute Myeloid Leukemia Cells. Int. J. Mol. Sci. 2016, 17, 1068. https://doi.org/10.3390/ijms17071068

AMA Style

Nachliely M, Sharony E, Bolla NR, Kutner A, Danilenko M. Prodifferentiation Activity of Novel Vitamin D2 Analogs PRI-1916 and PRI-1917 and Their Combinations with a Plant Polyphenol in Acute Myeloid Leukemia Cells. International Journal of Molecular Sciences. 2016; 17(7):1068. https://doi.org/10.3390/ijms17071068

Chicago/Turabian Style

Nachliely, Matan, Ehud Sharony, Narasimha R. Bolla, Andrzej Kutner, and Michael Danilenko. 2016. "Prodifferentiation Activity of Novel Vitamin D2 Analogs PRI-1916 and PRI-1917 and Their Combinations with a Plant Polyphenol in Acute Myeloid Leukemia Cells" International Journal of Molecular Sciences 17, no. 7: 1068. https://doi.org/10.3390/ijms17071068

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop