International Journal of Molecular Sciences | |
Antiproliferative Activity of Double Point Modified Analogs of 1,25-Dihydroxyvitamin D2 Against Human Malignant Melanoma Cell Lines | |
Anna Piotrowska3  Justyna Wierzbicka3  Sharmin Nadkarni4  Geoffrey Brown2  Andrzej Kutner4  Michał A. Żmijewski3  Roman Perez-Fernandez1  | |
[1] Department of Histology, Faculty of Medicine, Medical University of Gdańsk, 1a Debinki, Gdańsk 80-211, PolandSchool of Immunity and Infection, University of Birmingham, Vincent Drive, Edgbaston, Birmingham, West Midlands B15 2TT, UK;Department of Histology, Faculty of Medicine, Medical University of Gdańsk, 1a Debinki, Gdańsk 80-211, Poland;Pharmaceutical Research Institute, 8 Rydygiera, Warsaw 01-793, Poland; | |
关键词: vitamin D; vitamin D2; novel vitamin D analogs; melanoma; skin cancer; VDR; | |
DOI : 10.3390/ijms17010076 | |
来源: mdpi | |
【 摘 要 】
Vitamin D is a lipid soluble steroid hormone with pleiotropic biological properties, including regulation of cell proliferation, differentiation and apoptosis. As to these desirable anticancer actions, 1,25-dihydroxyvitamins D and analogs have been reported to inhibit the proliferation and to induce differentiation of a wide variety of cancer cell types, including human malignant melanoma. However, there is a need for novel and more efficacious vitamin D analogs, and how best to design such is still an open issue. A series of double point modified (DPM) analogs of 1,25-dihydroxyvitamin D2 (1,25(OH)2D2) induced differentiation of the vitamin D receptor (VDR) positive A375 and VDR negative SK-MEL 188b human malignant melanoma cell lines. Surprisingly, the dose of 1,25(OH)2D2 required to inhibit the proliferation of the A375 melanoma cell line by was several fold lower than that required in the case of 1,25(OH)2D3. To evaluate the impact of the modification in the side chain (additional 22-hydroxyl) and in the A-ring (5,6-trans modification), the regular side-chain of vitamin D2 or D3 was retained in the structure of our analogs. As expected, 5,6-
【 授权许可】
CC BY
© 2016 by the authors; licensee MDPI, Basel, Switzerland.
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