Antitumour effect of polyoxomolybdates: induction of apoptotic cell death and autophagy in in vitro and in vivo models

被引：0
作者：
A Ogata
H Yanagie
E Ishikawa
Y Morishita
S Mitsui
A Yamashita
K Hasumi
S Takamoto
T Yamase
M Eriguchi
机构：
[1] Chemical Resources Laboratory,Department of Nuclear Engineering and Management
[2] Tokyo Institute of Technology,Department of Pathology
[3] R1-21,Department of Molecular Health Sciences
[4] 4259 Nagatsuta Midori-ku Yokohama,Department of Cardiothoracic Surgery
[5] Cooperative Unit of Medicine and Engineering Research,Department of Microbiology
[6] The University of Tokyo Hospital,undefined
[7] 7-3-1 Hongo Bunkyo-ku,undefined
[8] School of Engineering,undefined
[9] The University of Tokyo,undefined
[10] 7-3-1 Hongo Bunkyo-ku,undefined
[11] Graduate School of Medicine,undefined
[12] The University of Tokyo,undefined
[13] 7-3-1 Hongo Bunkyo-ku,undefined
[14] Faculty of Pharmaceutical Sciences,undefined
[15] Teikyo University,undefined
[16] 1091-1 Suwarashi Sagamikochou Sagamihara,undefined
[17] Electro-Chemical and Cancer Research Institute,undefined
[18] 5-45-6 Kokuryo-cho Chofu,undefined
[19] Graduate School of Medicine,undefined
[20] University of Tokyo,undefined
[21] 7-3-1 Hongo Bunkyo-ku,undefined
[22] Showa University School of Pharmaceutical Sciences,undefined
[23] 1-5-8 Hatanodai Shinagawa-ku,undefined
来源：
British Journal of Cancer | 2008年 / 98卷
关键词：
polyoxomolybdate; apoptosis; autophagy;
D O I：
暂无
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学科分类号：
摘要：
Polyoxomolybdates (PMs) as discrete molybdenum-oxide cluster anions have been investigated in the course of study of their medical applications. Here, we show the significant antitumour potency of the polyoxomolybdate [Me3NH]6[H2MoV12O28(OH)12(MoVIO3)4]·2H2O (PM-17), which is a photo-reduced compound of [NH3Pri]6[Mo7O24]·3H2O. The effect of PM-17 on the growth of cancer cell lines and xenografts was assessed by a cell viability test and analysis of tumour expansion rate. Morphological analysis was carried out by Hoechst staining, flow-cytometric analysis of Annexin V staining, terminal deoxynucleotidyl transferase-mediated ‘nick-end’ labelling staining, and electron-microscopic analysis. Activation of autophagy was detected by western blotting and fluorescence-microscopic analysis of the localisation of GFP-LC3 in transfected tumour cells. PM-17 inhibited the growth of human pancreatic cancer (AsPC-1) xenografts in a nude mice model, and induced morphological alterations in tumour cells. Correspondingly, PM-17 repressed the proliferation of AsPC-1 cells and human gastric cancer cells (MKN45) depending on the dose in vitro. We observed apoptotic patterns as the formation of apoptotic small bodies and translocation of phosphatidylserine by Hoechst staining and flow-cytometric analysis following Annexin V staining, and in parallel, autophagic conformation by the formulation of autophagosomes and localisation of GFP-LC3 by electron- and fluorescence-microscopic analysis.
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页码：399 / 409
页数：10
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