title: Eldecalcitol (ED-71), an analog of 1α,25-dihydroxyvitamin D3 as a potential anti-cancer agent for oral squamous cell carcinomas.
abstract: We have previously reported that 1,25(OH)2D3inhibits NF-κB activity and thus inhibits growth of OSCC cells in serum-free culture and down-regulates HBp17/FGFBP-1 expression, which is important for cancer cell growth and angiogenesis. Here, we have investigated the effects of ED-71, an analog of vitamin D3 (VD) on OSCC cell lines in serum-free culture. It is known that ED-71 has a stronger inhibitory effect on bone resorption compared to VD and other VD analogs. To the best of our knowledge, there was no report examining the potential of ED-71 as an anti-cancer agent for OSCC. We found that ED-71 is able to inhibit the growth of cancer cell lines at a concentration of hundred times lower than calcitriol. As Cyp24A1 was reportedly induced in cancer cells, we measured the expression of CYP24A1 in OSCC cell lines (NA and UE), A431 epidermoid carcinoma and normal fibroblast cell (gfi) in serum-free culture. As a result, CYP24A1 mRNA and the protein expression in the OSCC cells treated with ED-71 increased in a dose-dependent manner. However, in vivo experiment, in which the A431 cells were implanted in mice, tumor formation was reduced by the ED-71 treatment with no significant difference between Cyp24A1 expression in the tumors of ED-71-treated and control group, as analyzed by western blotting and immunohistochemistry. These results suggest that ED-71 is a potential anti-cancer agent for OSCC.
authors.affiliation: Center of Oral Clinical Examination, Hiroshima University Hospital, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Shintani
authors.affiliation: Department of Molecular Oral Medicine & Maxillofacial Surgery, Graduate School of Biomedical & Health Sciences, Japan; Oral Cancer Research & Coordinating Center, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: S N Z
authors.initials: SNZ
authors.lastname: Rosli
authors.affiliation: Department of Molecular Oral Medicine & Maxillofacial Surgery, Graduate School of Biomedical & Health Sciences, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Takatsu
authors.affiliation: Oral Cancer Research & Coordinating Center, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Y F
authors.initials: YF
authors.lastname: Choon
authors.affiliation: Oral Maxillofacial Surgery, University Hospital, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashido
authors.affiliation: Department of Molecular Oral Medicine & Maxillofacial Surgery, Division of Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Toratani
authors.affiliation: Oral Maxillofacial Surgery, University Hospital, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Usui
authors.affiliation: Department of Molecular Oral Medicine & Maxillofacial Surgery, Division of Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan. Electronic address: tetsuok@hiroshima-u.ac.jp.
authors.forename: T
authors.initials: T
authors.lastname: Okamoto
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000737:chemistry; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D016895:Culture Media, Serum-Free; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism; D005881:Gingiva / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000188:drug therapy*; D009368:Neoplasm Transplantation; D014807:Vitamin D / Q000031:analogs & derivatives; D065668:Vitamin D3 24-Hydroxylase / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016895:Culture Media, Serum-Free; D014807:Vitamin D; C585549:CYP24A1 protein, human; C585550:Cyp24a1 protein, mouse; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol; C547512:eldecalcitol
keywords: 1,25(OH)(2)D(3); CYP24A1; Eldecalcitol(ED-71); Oral squamous cell carcinoma