Noncalcemic 20-hydroxyvitamin D3 inhibits human melanoma growth in in vitro and in vivo models
| Autor: | Cezary Skobowiat, Allen S.W. Oak, Lawrence M. Pfeffer, Chuan He Yang, Tae Kang Kim, Andrzej Slominski, Robert C. Tuckey |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
mice Skin Neoplasms Time Factors pre-clinical vitamin D Antineoplastic Agents Mice SCID Pharmacology Secosteroid 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo Cell Movement Mice Inbred NOD Cell Line Tumor Vitamin D and neurology melanoma Cell Adhesion Medicine Animals Humans Calcifediol Cell Proliferation Dose-Response Relationship Drug business.industry Melanoma Cancer SKMel-188 medicine.disease Xenograft Model Antitumor Assays In vitro 3. Good health Tumor Burden 030104 developmental biology Oncology chemistry 030220 oncology & carcinogenesis Pharmacodynamics Toxicity Immunology business Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Cezary Skobowiat 1, 2, * , Allen S.W. Oak 1, * , Tae-Kang Kim 1 , Chuan He Yang 3 , Lawrence M. Pfeffer 3 , Robert C. Tuckey 4 , Andrzej T. Slominski 1, 5, 6, 7 1 Department of Dermatology, University of Alabama at Birmingham, AL, USA 2 Department of Pharmacodynamics and Molecular Pharmacology, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University in Torun, Poland 3 Department of Pathology and Laboratory Medicine, and the Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN, USA 4 School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA, Australia 5 Laboratory Service of the VA Medical Center, Birmingham, AL, USA 6 Comprehensive Cancer Center Cancer Chemoprevention Program, University of Alabama at Birmingham, AL, USA 7 Nutrition Obesity Research Center, University of Alabama at Birmingham, AL, USA * These authors have contributed equally to this work Correspondence to: Andrzej T. Slominski, email: aslominski@uabmc.edu Keywords: melanoma, pre-clinical, SKMel-188, vitamin D, mice Received: September 09, 2016 Accepted: November 23, 2016 Published: December 26, 2016 ABSTRACT A novel pathway of vitamin D 3 (D 3 ) metabolism, initiated by C20-hydroxylation of D 3 by CYP11A1, has been confirmed to operate in vivo . Its major product, 20(OH)D 3 , exhibits antiproliferative activity in vitro comparable to that of 1,25(OH) 2 D 3, but is noncalcemic in mice and rats. To further characterize the antimelanoma activity of 20(OH)D 3 , we tested its effect on colony formation of human melanoma cells in monolayer culture and anchorage-independent growth in soft agar. The migratory capabilities of the cells and cell-cell and cell-extracellular matrix interactions were also evaluated using transwell cell migration and spheroid toxicity assays. To assess the antimelanoma activity of 20(OH)D 3 in vivo , age-matched immunocompromised mice were subcutaneously implanted with luciferase-labelled SKMel-188 cells and were randomly assigned to be treated with either 20(OH)D 3 or vehicle ( n =10 per group). Tumor size was measured with caliper and live bioimaging methods, and overall health condition expressed as a total body score scale. The following results were observed: (i) 20(OH)D 3 inhibited colony formation both in monolayer and soft agar conditions, (ii) 20(OH)D 3 inhibited melanoma cells in both transwell migration and spheroid toxicity assays, and (iii) 20(OH)D 3 inhibited melanoma tumor growth in immunocompromised mice without visible signs of toxicity. However, although the survival rate was 90% in both groups, the total body score was higher in the treatment group compared to control group (2.8 vs. 2.55). In conclusion, 20(OH)D 3 , an endogenously produced secosteroid, is an excellent candidate for further preclinical testing as an antimelanoma agent. |
| Databáze: | OpenAIRE |
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