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

Kun-Chun Chiang,Masashi Takano,Chi-Chin Sun,Li-Wei Chen,Horng-Heng Juang,Atsushi Kittaka,Chun-Nan Yeh,Ta-Sen Yeh,Jun-Te Hsu,Sheng-Fong Kuo,Tai Chen,Shin-Cheh Chen,Jong-Hwei Pang

doi:10.3390/ijms17040606

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.

Highlights

Breast cancer, the most common diagnosed cancer and second leading cause of death in women, has about 1 million new cases per year worldwide [1]
Triple-negative breast cancer (TNBC) features the lack of expression of estrogen and progesterone receptors and the lack of overexpression of HER-2, which result in the resistance to anti-hormone therapies and HER-2-aiming target therapies [6]
We aimed to investigate the effect of MART-10 on TNBC metastasis with the attempt to develop a new regimen for TNBC treatment

Summary

Introduction

The most common diagnosed cancer and second leading cause of death in women, has about 1 million new cases per year worldwide [1]. Approximately 25% to 50% of breast cancer patients would still develop metastasis eventually, leading to the poor prognosis [2,3]. Triple-negative breast cancer (TNBC) accounts for 12%–20% of all breast cancer and is with more aggressive disease progress and worse prognosis [4,5]. TNBC features the lack of expression of estrogen and progesterone receptors and the lack of overexpression of HER-2, which result in the resistance to anti-hormone therapies and HER-2-aiming target therapies [6]. Since most TNBC patients die of cancer metastasis, finding a new regiment to inhibit TNBC metastasis should be prioritized

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