RRC ID 43765
著者 Kitano T, Yoda H, Tabata K, Miura M, Toriyama M, Motohashi S, Suzuki T.
タイトル Vitamin K3 analogs induce selective tumor cytotoxicity in neuroblastoma.
ジャーナル Biol Pharm Bull
Abstract We investigated the cytotoxicity of eight vitamin K3 (VK3) analogs against neuroblastoma cell lines (IMR-32, LA-N-1, NB-39, and SK-N-SH) and normal cell lines (human umbilical vein endothelial cells (HUVEC) and human dermal fibroblasts (HDF)) using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. 2-[(2-Methoxy)ethylthio]-3-methyl-1,4-naphthoquinone (VK3-OCH(3)) showed especially potent cytotoxic activities against neuroblastoma cells compared with normal cells. In a Hoechst 33342 staining experiment, apoptotic morphologies characterized by cell shrinkage, nuclear condensation, and nuclear fragmentation were observed in IMR-32 and LA-N-1 cells after 48 h of treatment with 10(-5) M of VK3-OCH(3). To clarify the molecular mechanisms of apoptosis induced by VK3-OCH(3), we examined the expression of apoptosis related proteins using a Proteome Profiler Array and western blotting. Heme oxygenase (HO)-1 was remarkably increased by VK3-OCH(3) compared with the control (173% in IMR-32 and 170% in LA-N-1 at 24 h). Moreover, caveolin-1 was induced by VK3-OCH(3) at 48 h. In addition, VK3-OCH(3) arrested the cell cycle at the G2/M phase in IMR-32 cells. These results suggest that VK3-OCH(3) exhibited a selective antitumor activity via HO-1-related mechanisms.
巻・号 35(4)
ページ 617-23
公開日 2012-1-1
DOI 10.1248/bpb.35.617
PII JST.JSTAGE/bpb/35.617
PMID 22466570
MeSH Antineoplastic Agents / pharmacology* Caveolin 1 Cell Cycle / drug effects Cell Line, Tumor Cell Survival Fibroblasts / drug effects Fibroblasts / metabolism Fibroblasts / pathology Gene Expression Profiling Heme Oxygenase-1 Human Umbilical Vein Endothelial Cells Humans Neuroblastoma / drug therapy* Neuroblastoma / metabolism Neuroblastoma / pathology Proteome Vitamin K 3 / analogs & derivatives* Vitamin K 3 / pharmacology
IF 1.863
引用数 17
WOS 分野 PHARMACOLOGY & PHARMACY
リソース情報
ヒト・動物細胞 LA-N-1(RCB0483) SK-N-SH(RCB0426)