タキタ　モリチカ   Morichika Takita   瀧田　守親    所属   医学部 医学科    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	1α,25(OH)2 D3-26,23-lactam, a novel vitamin D3 analog, acts as a vitamin D3 antagonist in human prostate cancer cells.
掲載誌名	正式名：Journal of Health Science ISSNコード：13449702/13475207
掲載区分	国内
出版社	Pharmaceutical Society of JAPAN
巻・号・頁	54(4),pp.497-502
著者・共著者	Takita Morichika†, Hirata Michiko, Tsukamoto Kazuki, Nagasawa kazuo, Miyaura Chisato*, Inada Masaki
担当区分	筆頭著者
発行年月	2008/08
概要	1α,25-Dihydroxyvitamin D3 [1α,25(OH)2D3], the active form of vitamin D3, is known to exhibit an anti-tumor properties and markedly suppresses the growth of various human cancer cells. We synthesized novel vitamin D analogs, 1α,25-dihydroxyvitamin D3-26,23-lactam (DLAMs), having a lactam moiety in the side chain, and examined the effects on cell growth of human prostate cancer cells LNCaP. 1α,25(OH)2D3 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)2D3 in LNCaP cells. The effects of 1α,25(OH)2D3 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)2D3. The expression of p21 mRNA induced by 1α,25(OH)2D3 was suppressed by (23S,25S)-DLAM-1P but not by (23R,25R)-DLAM-1P in LNCaP cells. In the absence of 1α,25(OH)2D3, 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 D3 antagonist in cancer cells.
DOI	http://doi.org/10.1248/jhs.54.497