1α,25-Dihydroxyvitamin D_3-26,23-lactam, a Novel Vitamin D_3 Analog, Acts as a Vitamin D_3 Antagonist in Human Prostate Cancer Cells
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概要
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1α,25-Dihydroxyvitamin D_3 [1α,25(OH)_2D_3], the active form of vitamin D_3, is known to exhibit an anti-tumor properties and markedly suppresses the growth of various human cancer cells. We synthesized novel vitamin D analogs, lα,25-dihydroxyvitamin D_3-26,23-lactam (DLAMs), having a lactam moiety in the side chain, and examined the effects on cell growth of human prostate cancer cells LNCaP. lα,25(OH)_2D_3 significantly suppressed both the number of cells and cell viability. The mRNA expression of p21, well-known as a tumor suppressive gene, was clearly induced by treatment with 1α,25(OH)_2D_3 in LNCaP cells. The effects of 1α,25(OH)_2D_3 on the growth suppression of LNCaP cells was attenuated by the simultaneous addition of (23S,25S)-DLAM-1P. In a computer docking simulation, (23S,25S)-DLAM-1P bound to vitamin D receptor (VDR), and its lactam moiety may interfere VDR helix-12 folding. Its stereoisomer (23R,25R)-DLAM-1P did not influence cell growth regulated by 1α,25(OH)_2D_3. The expression of p21 mRNA induced by 1α,25(OH)_2D_3 was suppressed by (23S,25S)-DLAM-1P but not by (23R,25R)-DLAM-1P in LNCaP cells. In the absence of 1α,25(OH)_2D_3, neither (23S,25S)-DLAM-1P nor (23R,25R)-DLAM-1P regulated the cell growth of LNCaP cells. Thus, (23S,25S)-DLAM-1P interferes with the VDR signal and acts as a vitamin D_3 antagonist in cancer cells.
- 公益社団法人日本薬学会の論文
- 2008-08-01
著者
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Takita Morichika
Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology
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Inada Masaki
Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology
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Miyaura Chisato
Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology
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Inada Masaki
Dep. Of Biotechnology And Life Sci. Tokyo Univ. Of Agriculture And Technol.
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NAGASAWA Kazuo
Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology
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Nagasawa Kazuo
Department Of Biotechnology And Life Science Tokyo University Of Agriculture And Technology
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HIRATA Michiko
Department of Biochemistry and Molecular Biology, Tokyo University of Pharmacy and Life Scienc
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Hirata Michiko
Department Of Biochemistry And Molecular Biology Tokyo University Of Pharmacy And Life Scienc : Bio-
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Tsukamoto Kazuki
Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology
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Tsukamoto Kazuki
Department Of Biotechnology And Life Science Tokyo University Of Agriculture And Technology
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Miyaura Chisato
Department Of Biotechnology And Life Science Tokyo University Of Agriculture And Technology
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Nagasawa Kazuo
Department Of Biotechnology And Life Science Faculty Of Technology Tokyo University Of Agriculture A
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Takita Morichika
Department Of Biotechnology And Life Science Tokyo University Of Agriculture And Technology
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Hirata Michiko
Department Of Biotechnology And Life Science Tokyo University Of Agriculture And Technology
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Inada Masaki
Department Of Biotechnology And Life Science Tokyo University Of Agriculture And Technology
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Matsumoto Chiho
Department Of Biotechnology And Life Science Tokyo University Of Agriculture And Technology
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Miyaura C
Department Of Biotechnology And Life Science Tokyo University Of Agriculture And Technology
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MIYAURA CHISATO
Department of Biochemistry, School of Dentistry, Showa University
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NAGASAWA Kazuo
Department of Biochemical Engineering, Faculty of Pharmaceutical Sciences, Osaka University
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