1. ¹Chemical Resources Laboratory, Tokyo Institute of Technology, R1-21, 4259 Nagatsuta Midori-ku Yokohama, Tokyo 226-8503, Japan
2. ²Cooperative Unit of Medicine and Engineering Research, The University of Tokyo Hospital, 7-3-1 Hongo Bunkyo-ku, Tokyo 113-8655, Japan
3. ³Department of Nuclear Engineering and Management, School of Engineering, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo 113-8655, Japan
4. ⁴Department of Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo 113-8655, Japan
5. ⁵Department of Molecular Health Sciences, Faculty of Pharmaceutical Sciences, Teikyo University, 1091-1 Suwarashi Sagamikochou Sagamihara, Kanagawa 229-0195, Japan
6. ⁶Electro-Chemical and Cancer Research Institute, 5-45-6 Kokuryo-cho Chofu, Tokyo 182-0022, Japan
7. ⁷Department of Cardiothoracic Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo 113-8655, Japan
8. ⁸Department of Microbiology, Showa University School of Pharmaceutical Sciences, 1-5-8 Hatanodai Shinagawa-ku, Tokyo 142-8555, Japan

Correspondence: H Yanagie, E-mail: yanagie@n.t.u-tokyo.ac.jp

Revised 16 October 2007; Accepted 15 November 2007; Published online 18 December 2007.

Abstract

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[H₂Mo^V₁₂O₂₈(OH)₁₂(Mo^VIO₃)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.