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PRIMA-1(MET) Does Not Restore Vitamin D Sensitivity to MDA-MB-231 and MDA-MB-468 Triple-Negative Breast Cancer Cells

[Image: see text] Vitamin D is a steroid hormone that causes growth suppression in cultured cells. We had previously discovered that the triple-negative breast cancer cell lines MDA-MB-231 and MDA-MB-468 did not have growth suppression with vitamin D, while MCF-7 did. MCF-7 cells are not triple-nega...

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Autores principales: Kotob, Shadi N., Kelts, Jessica L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10448659/
https://www.ncbi.nlm.nih.gov/pubmed/37636961
http://dx.doi.org/10.1021/acsomega.3c03719
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author Kotob, Shadi N.
Kelts, Jessica L.
author_facet Kotob, Shadi N.
Kelts, Jessica L.
author_sort Kotob, Shadi N.
collection PubMed
description [Image: see text] Vitamin D is a steroid hormone that causes growth suppression in cultured cells. We had previously discovered that the triple-negative breast cancer cell lines MDA-MB-231 and MDA-MB-468 did not have growth suppression with vitamin D, while MCF-7 did. MCF-7 cells are not triple-negative and have wild-type p53. Both MDA-MB-231 and MDA-MB-468 have mutations in p53 and these mutations were a possible explanation for the lack of growth suppression with vitamin D. Our hypothesis was that reactivation of p53 in the triple-negative cell lines would cause them to become sensitive to vitamin D. We chose to use the small molecule PRIMA-1(MET) to reactivate p53 as it has been previously shown to restore function to the p53 mutants present in MB-231 and MB-468. We then measured the ability of vitamin D and its analogues calcipotriol and EB1089 to suppress growth in the presence of PRIMA-1(MET). Here, we show that while PRIMA-1(MET) can kill the breast cancer cells investigated in this study, it does not restore their sensitivity to vitamin D or its analogues.
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spelling pubmed-104486592023-08-25 PRIMA-1(MET) Does Not Restore Vitamin D Sensitivity to MDA-MB-231 and MDA-MB-468 Triple-Negative Breast Cancer Cells Kotob, Shadi N. Kelts, Jessica L. ACS Omega [Image: see text] Vitamin D is a steroid hormone that causes growth suppression in cultured cells. We had previously discovered that the triple-negative breast cancer cell lines MDA-MB-231 and MDA-MB-468 did not have growth suppression with vitamin D, while MCF-7 did. MCF-7 cells are not triple-negative and have wild-type p53. Both MDA-MB-231 and MDA-MB-468 have mutations in p53 and these mutations were a possible explanation for the lack of growth suppression with vitamin D. Our hypothesis was that reactivation of p53 in the triple-negative cell lines would cause them to become sensitive to vitamin D. We chose to use the small molecule PRIMA-1(MET) to reactivate p53 as it has been previously shown to restore function to the p53 mutants present in MB-231 and MB-468. We then measured the ability of vitamin D and its analogues calcipotriol and EB1089 to suppress growth in the presence of PRIMA-1(MET). Here, we show that while PRIMA-1(MET) can kill the breast cancer cells investigated in this study, it does not restore their sensitivity to vitamin D or its analogues. American Chemical Society 2023-08-08 /pmc/articles/PMC10448659/ /pubmed/37636961 http://dx.doi.org/10.1021/acsomega.3c03719 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Kotob, Shadi N.
Kelts, Jessica L.
PRIMA-1(MET) Does Not Restore Vitamin D Sensitivity to MDA-MB-231 and MDA-MB-468 Triple-Negative Breast Cancer Cells
title PRIMA-1(MET) Does Not Restore Vitamin D Sensitivity to MDA-MB-231 and MDA-MB-468 Triple-Negative Breast Cancer Cells
title_full PRIMA-1(MET) Does Not Restore Vitamin D Sensitivity to MDA-MB-231 and MDA-MB-468 Triple-Negative Breast Cancer Cells
title_fullStr PRIMA-1(MET) Does Not Restore Vitamin D Sensitivity to MDA-MB-231 and MDA-MB-468 Triple-Negative Breast Cancer Cells
title_full_unstemmed PRIMA-1(MET) Does Not Restore Vitamin D Sensitivity to MDA-MB-231 and MDA-MB-468 Triple-Negative Breast Cancer Cells
title_short PRIMA-1(MET) Does Not Restore Vitamin D Sensitivity to MDA-MB-231 and MDA-MB-468 Triple-Negative Breast Cancer Cells
title_sort prima-1(met) does not restore vitamin d sensitivity to mda-mb-231 and mda-mb-468 triple-negative breast cancer cells
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10448659/
https://www.ncbi.nlm.nih.gov/pubmed/37636961
http://dx.doi.org/10.1021/acsomega.3c03719
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