title: MART-10, a less calcemic vitamin D analog, is more potent than 1α,25-dihydroxyvitamin D3 in inhibiting the metastatic potential of MCF-7 breast cancer cells in vitro.
abstract: With the recent advance in breast cancer therapy, the survival rate of breast cancer patients has improved greatly. In spite of the progress, 25-50% of breast cancer patients eventually will develop metastasis. Due to limited early detection methods, metastasis is usually diagnosed at the late stages beyond recovery likely due to resistance to currently available breast cancer therapies. Thus, a new strategy to prevent cancer cell growth and repress tumor metastasis is desirable. The active form of vitamin D3, 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], has anti-invasion and anti-migration properties in pre-clinical studies, yet its clinical application has been hampered by its hypercalcemic side effect. Previously, we have demonstrated that a new class of less-calcemic vitamin D analog, 19-nor-2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D3 (MART-10), is 1000-fold more active than 1α,25(OH)2D3 in suppressing MCF-7 cells growth through cell cycle arrest and apoptosis induction. In the current study, we show for the first time that MART-10 is more active than 1α,25(OH)2D3 in preventing MCF-7 cell invasion and migration likely mediated through the upregulation of E-cadherin, and the downregulation of Snail, Slug, and Twist, the transcription factors implicated in epithelial-mesenchymal transition (EMT), as well as MMP-13. Based on the current in vitro and the highly anti-tumor characteristics of MART-10 in a pancreatic xenograft model, MART-10 is deemed as a promising candidate for breast cancer treatment. Further in vivo animal study comparing MART-10 with 1α,25(OH)2D3 and other potent and less calcemic analogs of vitamin D is warranted.
authors.affiliation: General Surgery Department, Chang Gung Memorial Hospital, 222, Mai-Chin Road, Keelung, Taiwan, ROC; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan, Taiwan, ROC.
authors.forename: Kun-Chun
authors.initials: KC
authors.lastname: Chiang
authors.forename: Shin-Cheh
authors.initials: SC
authors.lastname: Chen
authors.forename: Chun-Nan
authors.initials: CN
authors.lastname: Yeh
authors.forename: Jong-Hwei S
authors.initials: JH
authors.lastname: Pang
authors.forename: Shih-Che
authors.initials: SC
authors.lastname: Shen
authors.forename: Jun-Te
authors.initials: JT
authors.lastname: Hsu
authors.forename: Yu-Yin
authors.initials: YY
authors.lastname: Liu
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Chen
authors.forename: Sheng-Fong
authors.initials: SF
authors.lastname: Kuo
authors.forename: Masashi
authors.initials: M
authors.lastname: Takano
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kittaka
authors.forename: Chi-Chin
authors.initials: CC
authors.lastname: Sun
authors.forename: Horng-Heng
authors.initials: HH
authors.lastname: Juang
authors.forename: Tai C
authors.initials: TC
authors.lastname: Chen
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015820:Cadherins / Q000378:metabolism; D002465:Cell Movement; D002762:Cholecalciferol / Q000031:analogs & derivatives* / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015870:Gene Expression; D006801:Humans; D061986:MCF-7 Cells; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C569618:19-nor-2-(3-hydroxypropyl)-1,25-dihydroxyvitamin D3; D015703:Antigens, CD; D000970:Antineoplastic Agents; C513384:CDH1 protein, human; C050361:CDH2 protein, human; D015820:Cadherins; D009687:Nuclear Proteins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D002762:Cholecalciferol; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: 19-nor-2α-(3-hydroxypropyl)-1α,25(OH)(2)D(3); 1α,25(OH)(2)D; 1α,25-dihydroxyvitamin D; Breast cancer; EMT; FBS; Invasion; MART-10; MCF-7; Metastasis; Migration; VDR; Vitamin D analog; epithelial–mesenchymal transition; fetal bovine serum; vitamin D receptor