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

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 [Me(3)NH](6)[H(2)Mo(V)(12)O(28)(OH)(12)(Mo(VI)O(3))(4)].2H(2)O (PM-17), which is a...

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Bibliographic Details
Published in:British journal of cancer 2008-01, Vol.98 (2), p.399-409
Main Authors: OGATA, A, YANAGIE, H, ISHIKAWA, E, MORISHITA, Y, MITSUI, S, YAMASHITA, A, HASUMI, K, TAKAMOTO, S, YAMASE, T, ERIGUCHI, M
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - therapeutic use
Apoptosis - drug effects
Autophagy - drug effects
Biological and medical sciences
Cell death
Cell Death - drug effects
Cell Proliferation - drug effects
Female
Humans
Medical sciences
Mice
Mice, Inbred BALB C
Mice, Nude
Molybdenum - chemistry
Molybdenum - therapeutic use
Oxides - chemistry
Oxides - therapeutic use
Polymers - chemistry
Polymers - therapeutic use
Translational Therapeutics
Tumor Cells, Cultured
Tumors
Xenograft Model Antitumor Assays
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Summary: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 [Me(3)NH](6)[H(2)Mo(V)(12)O(28)(OH)(12)(Mo(VI)O(3))(4)].2H(2)O (PM-17), which is a photo-reduced compound of [NH(3)Pr(i)](6)[Mo(7)O(24)].3H(2)O. 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.
ISSN:0007-0920
1532-1827
DOI:10.1038/sj.bjc.6604133