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Int. J. Mol. Sci. 2016, 17(4), 606; doi:10.3390/ijms17040606

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

1
General Surgery Department and Zebrafish Center, Chang Gung Memorial Hospital, Chang Gung University, Keelung 20401, Taiwan
2
General Surgery Department, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 20401, Taiwan
3
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 20401, Taiwan
4
Department of Gastroenterology, Chang Gung Memorial Hospital, Chang Gung University, Keelung 20401, Taiwan
5
Department of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Chang Gung University, Keelung 20401, Taiwan
6
Faculty of Pharmaceutical Sciences, Teikyo University, Tokyo 13228, Japan
7
Endocrine Core Lab, Boston University School of Medicine, Boston, MA 02118, USA
8
Department of Ophthalmology, Chang Gung Memorial Hospital, Chang Gung University, Keelung 20401, Taiwan
9
Department of Anatomy, College of Medicine, Chang Gung University, Taoyuan 20401, Taiwan
10
Urology Department, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 20401, Taiwan
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Roman Perez-Fernandez
Received: 31 March 2016 / Revised: 14 April 2016 / Accepted: 18 April 2016 / Published: 21 April 2016
View Full-Text   |   Download PDF [3193 KB, uploaded 21 April 2016]   |  

Abstract

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)2D3), the newly-synthesized 1α,25(OH)2D3 analog, has been shown to be much more potent in cancer growth inhibition than 1α,25(OH)2D3 and be active in vivo without inducing obvious side effect. In this study, we demonstrated that both 1α,25(OH)2D3 and MART-10 could effectively repress TNBC cells migration and invasion with MART-10 more effective. MART-10 and 1α,25(OH)2D3 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)2D3 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)2D3 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. View Full-Text
Keywords: triple negative breast cancer; TNBC; MART-10; EMT; vitamin D triple negative breast cancer; TNBC; MART-10; EMT; vitamin D
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Chiang, K.-C.; Yeh, T.-S.; Chen, S.-C.; Pang, J.-H.S.; Yeh, C.-N.; Hsu, J.-T.; Chen, L.-W.; Kuo, S.-F.; Takano, M.; Kittaka, A.; Chen, T.C.; Sun, C.-C.; Juang, H.-H. The Vitamin D Analog, MART-10, Attenuates Triple Negative Breast Cancer Cells Metastatic Potential. Int. J. Mol. Sci. 2016, 17, 606.

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