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)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.
General Surgery Department and Zebrafish Center, Chang Gung Memorial Hospital, Chang Gung University, Keelung 20401, Taiwan. robertviolet6292@yahoo.com.tw.
Kun-Chun
KC
Chiang
General Surgery Department, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 20401, Taiwan. tsy471027@adm.cgmh.org.tw.
Ta-Sen
TS
Yeh
General Surgery Department, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 20401, Taiwan. chensc@adm.cgmh.org.tw.
Shin-Cheh
SC
Chen
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 20401, Taiwan. jonghwei@mail.cgu.edu.tw.
Jong-Hwei S
JH
Pang
General Surgery Department, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 20401, Taiwan. yehchunnan@gmail.com.
Chun-Nan
CN
Yeh
General Surgery Department, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 20401, Taiwan. hsujt2813@adm.cgmh.org.tw.
Jun-Te
JT
Hsu
Department of Gastroenterology, Chang Gung Memorial Hospital, Chang Gung University, Keelung 20401, Taiwan. leiwei@adm.cgmh.org.tw.
Li-Wei
LW
Chen
Department of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Chang Gung University, Keelung 20401, Taiwan. shengfoung@gmail.com.
Sheng-Fong
SF
Kuo
Faculty of Pharmaceutical Sciences, Teikyo University, Tokyo 13228, Japan. mtakano@pharm.teikyo-u.ac.jp.
Masashi
M
Takano
Faculty of Pharmaceutical Sciences, Teikyo University, Tokyo 13228, Japan. akittaka@pharm.teikyo-u.ac.jp.
Atsushi
A
Kittaka
Endocrine Core Lab, Boston University School of Medicine, Boston, MA 02118, USA. taichen@bu.edu.
Tai C
TC
Chen
Department of Ophthalmology, Chang Gung Memorial Hospital, Chang Gung University, Keelung 20401, Taiwan. arvin.sun@msa.hinet.net.
Chi-Chin
CC
Sun
Department of Anatomy, College of Medicine, Chang Gung University, Taoyuan 20401, Taiwan. hhj143@mail.cgu.edu.tw.|Urology Department, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 20401, Taiwan. hhj143@mail.cgu.edu.tw.
Horng-Heng
HH
Juang
D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002762:Cholecalciferol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000517:prevention & control; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*
C569618:19-nor-2-(3-hydroxypropyl)-1,25-dihydroxyvitamin D3; D015820:Cadherins; D002762:Cholecalciferol
EMT; MART-10; TNBC; triple negative breast cancer; vitamin D