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The Vitamin D Analog, MART-10, Attenuates Triple Negative Breast Cancer Cells Metastatic Potential

Regarding breast cancer treatment, triple negative breast cancer (TNBC) is a difficult issue. Most TNBC patients die of cancer metastasis. Thus, to develop a new regimen to attenuate TNBC metastatic potential is urgently needed. MART-10 (19-nor-2α-(3-hydroxypropyl)-1α,25(OH)(2)D(3)), the newly-synth...

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Autores principales: Chiang, Kun-Chun, Yeh, Ta-Sen, Chen, Shin-Cheh, Pang, Jong-Hwei S., Yeh, Chun-Nan, Hsu, Jun-Te, Chen, Li-Wei, Kuo, Sheng-Fong, Takano, Masashi, Kittaka, Atsushi, Chen, Tai C., Sun, Chi-Chin, Juang, Horng-Heng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849057/
https://www.ncbi.nlm.nih.gov/pubmed/27110769
http://dx.doi.org/10.3390/ijms17040606
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author Chiang, Kun-Chun
Yeh, Ta-Sen
Chen, Shin-Cheh
Pang, Jong-Hwei S.
Yeh, Chun-Nan
Hsu, Jun-Te
Chen, Li-Wei
Kuo, Sheng-Fong
Takano, Masashi
Kittaka, Atsushi
Chen, Tai C.
Sun, Chi-Chin
Juang, Horng-Heng
author_facet Chiang, Kun-Chun
Yeh, Ta-Sen
Chen, Shin-Cheh
Pang, Jong-Hwei S.
Yeh, Chun-Nan
Hsu, Jun-Te
Chen, Li-Wei
Kuo, Sheng-Fong
Takano, Masashi
Kittaka, Atsushi
Chen, Tai C.
Sun, Chi-Chin
Juang, Horng-Heng
author_sort Chiang, Kun-Chun
collection PubMed
description Regarding breast cancer treatment, triple negative breast cancer (TNBC) is a difficult issue. Most TNBC patients die of cancer metastasis. Thus, to develop a new regimen to attenuate TNBC metastatic potential is urgently needed. MART-10 (19-nor-2α-(3-hydroxypropyl)-1α,25(OH)(2)D(3)), the newly-synthesized 1α,25(OH)(2)D(3) analog, has been shown to be much more potent in cancer growth inhibition than 1α,25(OH)(2)D(3) and be active in vivo without inducing obvious side effect. In this study, we demonstrated that both 1α,25(OH)(2)D(3) and MART-10 could effectively repress TNBC cells migration and invasion with MART-10 more effective. MART-10 and 1α,25(OH)(2)D(3) induced cadherin switching (upregulation of E-cadherin and downregulation of N-cadherin) and downregulated P-cadherin expression in MDA-MB-231 cells. The EMT(epithelial mesenchymal transition) process in MDA-MB-231 cells was repressed by MART-10 through inhibiting Zeb1, Zeb2, Slug, and Twist expression. LCN2, one kind of breast cancer metastasis stimulator, was also found for the first time to be repressed by 1α,25(OH)(2)D(3) and MART-10 in breast cancer cells. Matrix metalloproteinase-9 (MMP-9) activity was also downregulated by MART-10. Furthermore, F-actin synthesis in MDA-MB-231 cells was attenuated as exposure to 1α,25(OH)(2)D(3) and MART-10. Based on our result, we conclude that MART-10 could effectively inhibit TNBC cells metastatic potential and deserves further investigation as a new regimen to treat TNBC.
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spelling pubmed-48490572016-05-04 The Vitamin D Analog, MART-10, Attenuates Triple Negative Breast Cancer Cells Metastatic Potential Chiang, Kun-Chun Yeh, Ta-Sen Chen, Shin-Cheh Pang, Jong-Hwei S. Yeh, Chun-Nan Hsu, Jun-Te Chen, Li-Wei Kuo, Sheng-Fong Takano, Masashi Kittaka, Atsushi Chen, Tai C. Sun, Chi-Chin Juang, Horng-Heng Int J Mol Sci Article Regarding breast cancer treatment, triple negative breast cancer (TNBC) is a difficult issue. Most TNBC patients die of cancer metastasis. Thus, to develop a new regimen to attenuate TNBC metastatic potential is urgently needed. MART-10 (19-nor-2α-(3-hydroxypropyl)-1α,25(OH)(2)D(3)), the newly-synthesized 1α,25(OH)(2)D(3) analog, has been shown to be much more potent in cancer growth inhibition than 1α,25(OH)(2)D(3) and be active in vivo without inducing obvious side effect. In this study, we demonstrated that both 1α,25(OH)(2)D(3) and MART-10 could effectively repress TNBC cells migration and invasion with MART-10 more effective. MART-10 and 1α,25(OH)(2)D(3) induced cadherin switching (upregulation of E-cadherin and downregulation of N-cadherin) and downregulated P-cadherin expression in MDA-MB-231 cells. The EMT(epithelial mesenchymal transition) process in MDA-MB-231 cells was repressed by MART-10 through inhibiting Zeb1, Zeb2, Slug, and Twist expression. LCN2, one kind of breast cancer metastasis stimulator, was also found for the first time to be repressed by 1α,25(OH)(2)D(3) and MART-10 in breast cancer cells. Matrix metalloproteinase-9 (MMP-9) activity was also downregulated by MART-10. Furthermore, F-actin synthesis in MDA-MB-231 cells was attenuated as exposure to 1α,25(OH)(2)D(3) and MART-10. Based on our result, we conclude that MART-10 could effectively inhibit TNBC cells metastatic potential and deserves further investigation as a new regimen to treat TNBC. MDPI 2016-04-21 /pmc/articles/PMC4849057/ /pubmed/27110769 http://dx.doi.org/10.3390/ijms17040606 Text en © 2016 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
Chiang, Kun-Chun
Yeh, Ta-Sen
Chen, Shin-Cheh
Pang, Jong-Hwei S.
Yeh, Chun-Nan
Hsu, Jun-Te
Chen, Li-Wei
Kuo, Sheng-Fong
Takano, Masashi
Kittaka, Atsushi
Chen, Tai C.
Sun, Chi-Chin
Juang, Horng-Heng
The Vitamin D Analog, MART-10, Attenuates Triple Negative Breast Cancer Cells Metastatic Potential
title The Vitamin D Analog, MART-10, Attenuates Triple Negative Breast Cancer Cells Metastatic Potential
title_full The Vitamin D Analog, MART-10, Attenuates Triple Negative Breast Cancer Cells Metastatic Potential
title_fullStr The Vitamin D Analog, MART-10, Attenuates Triple Negative Breast Cancer Cells Metastatic Potential
title_full_unstemmed The Vitamin D Analog, MART-10, Attenuates Triple Negative Breast Cancer Cells Metastatic Potential
title_short The Vitamin D Analog, MART-10, Attenuates Triple Negative Breast Cancer Cells Metastatic Potential
title_sort vitamin d analog, mart-10, attenuates triple negative breast cancer cells metastatic potential
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849057/
https://www.ncbi.nlm.nih.gov/pubmed/27110769
http://dx.doi.org/10.3390/ijms17040606
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