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

J 2020

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

PAUKOVČEKOVÁ, Silvia, Dalibor VALÍK, Jaroslav ŠTĚRBA and Renata VESELSKÁ

Basic information

Original name

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

Authors

PAUKOVČEKOVÁ, Silvia (703 Slovakia, belonging to the institution), Dalibor VALÍK (203 Czech Republic, belonging to the institution), Jaroslav ŠTĚRBA (203 Czech Republic, belonging to the institution) and Renata VESELSKÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

International Journal of Molecular Sciences, Basel, MDPI, 2020, 1422-0067

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10603 Genetics and heredity

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.923

RIV identification code

RIV/00216224:14310/20:00117247

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.3390/ijms21186591

UT WoS

000580121900001

Keywords in English

osteosarcoma; calcitriol; calcidiol; all-transretinoic acid; vitamin D receptor; retinoic acid receptor alpha

Abstract

V originále

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-transretinoic 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 alpha (RAR alpha). 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 RAR alpha and VDR could be used as a predictor of possible synergy between ATRA and calcitriol in osteosarcoma cells.

Links

LM2018128, research and development project

Name: Český národní uzel Evropské sítě infrastruktur klinického výzkumu (Acronym: CZECRIN)

Investor: Ministry of Education, Youth and Sports of the CR

MUNI/A/1409/2019, interní kód MU

Name: Personalizovaná léčba v dětské onkologii: na cestě k "liquid dynamic medicine" a "N-of-1 clinical trials"

Investor: Masaryk University, Category A

Citovat

PAUKOVČEKOVÁ, Silvia, Dalibor VALÍK, Jaroslav ŠTĚRBA and Renata VESELSKÁ. Enhanced Antiproliferative Effect of Combined Treatment with Calcitriol and All-Trans Retinoic Acid in Relation to Vitamin D Receptor and Retinoic Acid Receptor alpha Expression in Osteosarcoma Cell Lines. International Journal of Molecular Sciences. Basel: MDPI, 2020, vol. 21, No 18, p. 1-19. ISSN 1422-0067. Available from: https://dx.doi.org/10.3390/ijms21186591.

@article{1705176,
   author = {Paukovčeková, Silvia and Valík, Dalibor and Štěrba, Jaroslav and Veselská, Renata},
   article_location = {Basel},
   article_number = {18},
   doi = {http://dx.doi.org/10.3390/ijms21186591},
   keywords = {osteosarcoma; calcitriol; calcidiol; all-transretinoic acid; vitamin D receptor; retinoic acid receptor alpha},
   language = {eng},
   issn = {1422-0067},
   journal = {International Journal of Molecular Sciences},
   title = {Enhanced Antiproliferative Effect of Combined Treatment with Calcitriol and All-Trans Retinoic Acid in Relation to Vitamin D Receptor and Retinoic Acid Receptor alpha Expression in Osteosarcoma Cell Lines},
   url = {https://doi.org/10.3390/ijms21186591},
   volume = {21},
   year = {2020}
}

TY  - JOUR
ID  - 1705176
AU  - Paukovčeková, Silvia - Valík, Dalibor - Štěrba, Jaroslav - Veselská, Renata
PY  - 2020
TI  - Enhanced Antiproliferative Effect of Combined Treatment with Calcitriol and All-Trans Retinoic Acid in Relation to Vitamin D Receptor and Retinoic Acid Receptor alpha Expression in Osteosarcoma Cell Lines
JF  - International Journal of Molecular Sciences
VL  - 21
IS  - 18
SP  - 1-19
EP  - 1-19
PB  - MDPI
SN  - 14220067
KW  - osteosarcoma
KW  - calcitriol
KW  - calcidiol
KW  - all-transretinoic acid
KW  - vitamin D receptor
KW  - retinoic acid receptor alpha
UR  - https://doi.org/10.3390/ijms21186591
L2  - https://doi.org/10.3390/ijms21186591
N2  - 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-transretinoic 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 alpha (RAR alpha). 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 RAR alpha and VDR could be used as a predictor of possible synergy between ATRA and calcitriol in osteosarcoma cells.
ER  -

PAUKOVČEKOVÁ, Silvia, Dalibor VALÍK, Jaroslav ŠTĚRBA and Renata VESELSKÁ. Enhanced Antiproliferative Effect of Combined Treatment with Calcitriol and All-Trans Retinoic Acid in Relation to Vitamin D Receptor and Retinoic Acid Receptor alpha Expression in Osteosarcoma Cell Lines. \textit{International Journal of Molecular Sciences}. Basel: MDPI, 2020, vol.~21, No~18, p.~1-19. ISSN~1422-0067. Available from: https://dx.doi.org/10.3390/ijms21186591.

Detailed Information on Publication Record