scholarly journals Enhanced Antiproliferative Effect of Combined Treatment with Calcitriol and All-Trans Retinoic Acid in Relation to Vitamin D Receptor and Retinoic Acid Receptor α Expression in Osteosarcoma Cell Lines

2020 ◽  
Vol 21 (18) ◽  
pp. 6591
Author(s):  
Silvia Paukovcekova ◽  
Dalibor Valik ◽  
Jaroslav Sterba ◽  
Renata Veselska
Keyword(s):  
Retinoic Acid ◽  
Cell Lines ◽  
Retinoic Acid Receptor ◽  
Combined Treatment ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Retinoic Acid Receptor Α

The main objective of this study was to analyze changes in the antiproliferative effect of vitamin D3, in the form of calcitriol and calcidiol, via its combined application with all-trans retinoic acid (ATRA) in osteosarcoma cell lines. The response to treatment with calcitriol and calcidiol alone was specific for each cell line. Nevertheless, we observed an enhanced effect of combined treatment with ATRA and calcitriol in the majority of the cell lines. Although the levels of respective nuclear receptors did not correlate with the sensitivity of cells to these drugs, vitamin D receptor (VDR) upregulation induced by ATRA was found in cell lines that were the most sensitive to the combined treatment. In addition, all these cell lines showed high endogenous levels of retinoic acid receptor α (RARα). Our study confirmed that the combination of calcitriol and ATRA can achieve enhanced antiproliferative effects in human osteosarcoma cell lines in vitro. Moreover, we provide the first evidence that ATRA is able to upregulate VDR expression in human osteosarcoma cells. According to our results, the endogenous levels of RARα and VDR could be used as a predictor of possible synergy between ATRA and calcitriol in osteosarcoma cells.

Pharicin B stabilizes retinoic acid receptor-α and presents synergistic differentiation induction with ATRA in myeloid leukemic cells

Blood ◽  
2010 ◽  
Vol 116 (24) ◽  
pp. 5289-5297 ◽  
Author(s):  
Zhi-Min Gu ◽  
Ying-Li Wu ◽  
Mei-Yi Zhou ◽  
Chuan-Xu Liu ◽  
Han-Zhang Xu ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Cell Lines ◽  
Retinoic Acid Receptor ◽  
Promyelocytic Leukemia ◽  
Leukemic Cells ◽  
Natural Ligand ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Induction Of Differentiation ◽  
Retinoic Acid Receptor Α

Abstract All-trans retinoic acid (ATRA), a natural ligand for the retinoic acid receptors (RARs), induces clinical remission in most acute promyelocytic leukemia (APL) patients through the induction of differentiation and/or eradication of leukemia-initiating cells. Here, we identify a novel natural ent-kaurene diterpenoid derived from Isodon pharicus leaves, called pharicin B, that can rapidly stabilize RAR-α protein in various acute myeloid leukemic (AML) cell lines and primary leukemic cells from AML patients, even in the presence of ATRA, which is known to induce the loss of RAR-α protein. Pharicin B also enhances ATRA-dependent the transcriptional activity of RAR-α protein in the promyelocytic leukemia–RARα–positive APL cell line NB4 cells. We also showed that pharicin B presents a synergistic or additive differentiation-enhancing effect when used in combination with ATRA in several AML cell lines and, especially, some primary leukemic cells from APL patients. In addition, pharicin B can overcome retinoid resistance in 2 of 3 NB4-derived ATRA-resistant subclones. These findings provide a good example for chemical biology–based investigations of pathophysiological and therapeutic significances of RAR-α and PML-RAR-α proteins. The effectiveness of the ATRA/pharicin B combination warrants further investigation on their use as a therapeutic strategy for AML patients.

scholarly journals CCAAT/enhancer binding proteins alpha and epsilon cooperate with all-trans retinoic acid in therapy but differ in their antileukemic activities

Blood ◽  
2006 ◽  
Vol 108 (7) ◽  
pp. 2416-2419 ◽  
Author(s):  
Young-Jin Lee ◽  
Letetia C. Jones ◽  
Nikolai A. Timchenko ◽  
Danilo Perrotti ◽  
Daniel G. Tenen ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Binding Proteins ◽  
Retinoic Acid Receptor ◽  
Chromosomal Translocation ◽  
Promyelocytic Leukemia ◽  
Leukemic Cells ◽  
Enhancer Binding Proteins ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Retinoic Acid Receptor Α

Abstract CCAAT/enhancer binding proteins (C/EBPs) play critical roles in myelopoiesis. Dysregulation of these proteins likely contributes to the pathogenesis of myeloid disorders characterized by a block in granulopoiesis. In one such disease, acute promyelocytic leukemia (APL), a promyelocytic leukemia–retinoic acid receptor α (PML-RARα) fusion protein is expressed as a result of a t(15;17) chromosomal translocation. Treatment of PML-RARα leukemic cells with all-trans retinoic acid (ATRA) causes them to differentiate into mature neutrophils, an effect thought to be mediated by C/EBPs. In this study, we assess the potential for cooperativity between increased C/EBP activity and ATRA therapy. We demonstrate that although both C/EBPα and C/EBPϵ can significantly prolong survival in a mouse model of APL, they are not functionally equivalent in this capacity. We also show that forced expression of C/EBPα or C/EBPϵ in combination with ATRA treatment has a synergistic effect on survival of leukemic mice compared with either therapy alone.

LOX/COX inhibitors enhance the antineoplastic effects of all-trans retinoic acid in osteosarcoma cell lines

Tumor Biology ◽  
2014 ◽  
Vol 35 (8) ◽  
pp. 7617-7627 ◽  
Author(s):  
Miroslava Krzyzankova ◽  
Silvia Chovanova ◽  
Petr Chlapek ◽  
Matej Radsetoulal ◽  
Jakub Neradil ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Cell Lines ◽  
Osteosarcoma Cell ◽  
Cox Inhibitors ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid
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