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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-7967212 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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