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Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models

1,25-Dihydroxycholecalciferol, the hormonally active vitamin D(3) metabolite, is known to exhibit therapeutic effects against breast cancer, mainly by lowering the expression of estrogen receptors and aromatase activity. Previously, the safety of the vitamin D active metabolite (24R)-1,24-dihydroxyc...

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Autores principales: Filip-Psurska, Beata, Psurski, Mateusz, Anisiewicz, Artur, Libako, Patrycja, Zbrojewicz, Ewa, Maciejewska, Magdalena, Chodyński, Michał, Kutner, Andrzej, Wietrzyk, Joanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967212/
https://www.ncbi.nlm.nih.gov/pubmed/33803480
http://dx.doi.org/10.3390/ijms22052781
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author Filip-Psurska, Beata
Psurski, Mateusz
Anisiewicz, Artur
Libako, Patrycja
Zbrojewicz, Ewa
Maciejewska, Magdalena
Chodyński, Michał
Kutner, Andrzej
Wietrzyk, Joanna
author_facet Filip-Psurska, Beata
Psurski, Mateusz
Anisiewicz, Artur
Libako, Patrycja
Zbrojewicz, Ewa
Maciejewska, Magdalena
Chodyński, Michał
Kutner, Andrzej
Wietrzyk, Joanna
author_sort Filip-Psurska, Beata
collection PubMed
description 1,25-Dihydroxycholecalciferol, the hormonally active vitamin D(3) metabolite, is known to exhibit therapeutic effects against breast cancer, mainly by lowering the expression of estrogen receptors and aromatase activity. Previously, the safety of the vitamin D active metabolite (24R)-1,24-dihydroxycholecalciferol (PRI-2191) and 1,25(OH)(2)D(3) analog PRI-2205 was tested, and the in vitro activity of these analogs against different cancer cell lines was studied. We determined the effect of the two vitamin D compounds on anastrozole (An) activity against breast cancer based on antiproliferative activity, ELISA, flow cytometry, enzyme inhibition potency, PCR, and xenograft study. Both the vitamin D active metabolite and synthetic analog regulated the growth of not only estrogen receptor-positive cells (T47D and MCF-7, in vitro and in vivo), but also hormone-independent cancer cells such as SKBR-3 (HER-2-positive) and MDA-MB-231 (triple-negative), despite their relatively low VDR expression. Combined with An, PRI-2191 and PRI-2205 significantly inhibited the tumor growth of MCF-7 cells. Potentiation of the antitumor activity in combined treatment of MCF-7 tumor-bearing mice is related to the reduced activity of aromatase by both An (enzyme inhibition) and vitamin D compounds (switched off/decreased aromatase gene expression, decreased expression of other genes related to estrogen signaling) and by regulation of the expression of the estrogen receptor ERα and VDR.
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spelling pubmed-79672122021-03-18 Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models Filip-Psurska, Beata Psurski, Mateusz Anisiewicz, Artur Libako, Patrycja Zbrojewicz, Ewa Maciejewska, Magdalena Chodyński, Michał Kutner, Andrzej Wietrzyk, Joanna Int J Mol Sci Article 1,25-Dihydroxycholecalciferol, the hormonally active vitamin D(3) metabolite, is known to exhibit therapeutic effects against breast cancer, mainly by lowering the expression of estrogen receptors and aromatase activity. Previously, the safety of the vitamin D active metabolite (24R)-1,24-dihydroxycholecalciferol (PRI-2191) and 1,25(OH)(2)D(3) analog PRI-2205 was tested, and the in vitro activity of these analogs against different cancer cell lines was studied. We determined the effect of the two vitamin D compounds on anastrozole (An) activity against breast cancer based on antiproliferative activity, ELISA, flow cytometry, enzyme inhibition potency, PCR, and xenograft study. Both the vitamin D active metabolite and synthetic analog regulated the growth of not only estrogen receptor-positive cells (T47D and MCF-7, in vitro and in vivo), but also hormone-independent cancer cells such as SKBR-3 (HER-2-positive) and MDA-MB-231 (triple-negative), despite their relatively low VDR expression. Combined with An, PRI-2191 and PRI-2205 significantly inhibited the tumor growth of MCF-7 cells. Potentiation of the antitumor activity in combined treatment of MCF-7 tumor-bearing mice is related to the reduced activity of aromatase by both An (enzyme inhibition) and vitamin D compounds (switched off/decreased aromatase gene expression, decreased expression of other genes related to estrogen signaling) and by regulation of the expression of the estrogen receptor ERα and VDR. MDPI 2021-03-09 /pmc/articles/PMC7967212/ /pubmed/33803480 http://dx.doi.org/10.3390/ijms22052781 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Filip-Psurska, Beata
Psurski, Mateusz
Anisiewicz, Artur
Libako, Patrycja
Zbrojewicz, Ewa
Maciejewska, Magdalena
Chodyński, Michał
Kutner, Andrzej
Wietrzyk, Joanna
Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models
title Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models
title_full Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models
title_fullStr Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models
title_full_unstemmed Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models
title_short Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models
title_sort vitamin d compounds pri-2191 and pri-2205 enhance anastrozole activity in human breast cancer models
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967212/
https://www.ncbi.nlm.nih.gov/pubmed/33803480
http://dx.doi.org/10.3390/ijms22052781
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