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

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.

• Authors: Kun-Chun Chiang, Ta-Sen Yeh, Shin-Cheh Chen, Jong-Hwei S Pang, Chun-Nan Yeh, Jun-Te Hsu, Li-Wei Chen, Sheng-Fong Kuo, Masashi Takano, Atsushi Kittaka, Tai C Chen, Chi-Chin Sun, Horng-Heng Juang
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 17 Issue 4 (Apr 21 2016) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 27110769 (Publication Type: Journal Article)

Chemical References

• 19-nor-2-(3-hydroxypropyl)-1,25-dihydroxyvitamin D3
• Cadherins
• Cholecalciferol

Topics

• Cadherins (genetics, metabolism)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cholecalciferol (analogs & derivatives, pharmacology, therapeutic use)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Neoplasm Invasiveness
• Neoplasm Metastasis (prevention & control)
• Triple Negative Breast Neoplasms (drug therapy, pathology)