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New Selective Progesterone Receptor Modulators and Their Impact on the RANK/RANKL Complex Activity
Breast cancer depends on women’s age. Its chemotherapy and hormone therapy lead to the loss of bone density and disruption of the skeleton. The proteins RANK and RANKL play a pivotal role in the formation of osteoclasts. It is also well established that the same proteins (RANK and RANKL) are the mai...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144723/ https://www.ncbi.nlm.nih.gov/pubmed/32183159 http://dx.doi.org/10.3390/molecules25061321 |
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author | Błaszczak-Świątkiewicz, Katarzyna |
author_facet | Błaszczak-Świątkiewicz, Katarzyna |
author_sort | Błaszczak-Świątkiewicz, Katarzyna |
collection | PubMed |
description | Breast cancer depends on women’s age. Its chemotherapy and hormone therapy lead to the loss of bone density and disruption of the skeleton. The proteins RANK and RANKL play a pivotal role in the formation of osteoclasts. It is also well established that the same proteins (RANK and RANKL) are the main molecules that play an important role in mammary stem cell biology. Mammary stem cells guarantee differentiation of the epithelial mammary cells, the growth of which is regulated by the progesterone-induced RANKL signaling pathway. The crosstalk between progesterone receptor, stimulated by progesterone and its analogues results in RANKL to RANK binding and activation of cell proliferation and subsequently unlimited expansion of the breast cancer cells. Therefore downstream regulation of this signaling pathway is desirable. To meet this need, a new class of selective estrogen receptor modulators (SPRMs) with anti- and mesoprogestin function were tested as potential anti-RANK agents. To establish the new feature of SPRMs, the impact of tested SPRMs on RANK-RANKL proteins interaction was tested. Furthermore, the cells proliferation upon RANKL stimulation, as well as NFkB and cyclin D1 expression, induced by tested SPRMs were analyzed. Conducted experiments proved NFkB expression inhibition as well as cyclin D1 expression limitation under asoprisnil and ulipristal treatment. The established paracrine anti-proliferative activity of antiprogestins together with competitive interaction with RANK make this class of compounds attractive for further study in order to deliver more evidence of their anti-RANK activity and potential application in the breast cancer therapy together with its accompanied osteoporosis. |
format | Online Article Text |
id | pubmed-7144723 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-71447232020-04-15 New Selective Progesterone Receptor Modulators and Their Impact on the RANK/RANKL Complex Activity Błaszczak-Świątkiewicz, Katarzyna Molecules Article Breast cancer depends on women’s age. Its chemotherapy and hormone therapy lead to the loss of bone density and disruption of the skeleton. The proteins RANK and RANKL play a pivotal role in the formation of osteoclasts. It is also well established that the same proteins (RANK and RANKL) are the main molecules that play an important role in mammary stem cell biology. Mammary stem cells guarantee differentiation of the epithelial mammary cells, the growth of which is regulated by the progesterone-induced RANKL signaling pathway. The crosstalk between progesterone receptor, stimulated by progesterone and its analogues results in RANKL to RANK binding and activation of cell proliferation and subsequently unlimited expansion of the breast cancer cells. Therefore downstream regulation of this signaling pathway is desirable. To meet this need, a new class of selective estrogen receptor modulators (SPRMs) with anti- and mesoprogestin function were tested as potential anti-RANK agents. To establish the new feature of SPRMs, the impact of tested SPRMs on RANK-RANKL proteins interaction was tested. Furthermore, the cells proliferation upon RANKL stimulation, as well as NFkB and cyclin D1 expression, induced by tested SPRMs were analyzed. Conducted experiments proved NFkB expression inhibition as well as cyclin D1 expression limitation under asoprisnil and ulipristal treatment. The established paracrine anti-proliferative activity of antiprogestins together with competitive interaction with RANK make this class of compounds attractive for further study in order to deliver more evidence of their anti-RANK activity and potential application in the breast cancer therapy together with its accompanied osteoporosis. MDPI 2020-03-13 /pmc/articles/PMC7144723/ /pubmed/32183159 http://dx.doi.org/10.3390/molecules25061321 Text en © 2020 by the author. 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 Błaszczak-Świątkiewicz, Katarzyna New Selective Progesterone Receptor Modulators and Their Impact on the RANK/RANKL Complex Activity |
title | New Selective Progesterone Receptor Modulators and Their Impact on the RANK/RANKL Complex Activity |
title_full | New Selective Progesterone Receptor Modulators and Their Impact on the RANK/RANKL Complex Activity |
title_fullStr | New Selective Progesterone Receptor Modulators and Their Impact on the RANK/RANKL Complex Activity |
title_full_unstemmed | New Selective Progesterone Receptor Modulators and Their Impact on the RANK/RANKL Complex Activity |
title_short | New Selective Progesterone Receptor Modulators and Their Impact on the RANK/RANKL Complex Activity |
title_sort | new selective progesterone receptor modulators and their impact on the rank/rankl complex activity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144723/ https://www.ncbi.nlm.nih.gov/pubmed/32183159 http://dx.doi.org/10.3390/molecules25061321 |
work_keys_str_mv | AT błaszczakswiatkiewiczkatarzyna newselectiveprogesteronereceptormodulatorsandtheirimpactontherankranklcomplexactivity |