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

Ogata A, Yanagie H, Ishikawa E, Morishita Y, Mitsui S, Yamashita A, Hasumi K, Takamoto S, Yamase T, Eriguchi M - Br. J. Cancer (2007)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Chemical Resources Laboratory, Tokyo Institute of Technology, R1-21, 4259 Nagatsuta Midori-ku Yokohama, Tokyo 226-8503, Japan.

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 [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.

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The effect of PM-17 treatment on MKN45 cell and AsPC-1 cell survival in vitro. MKN45 cells were treated with PM-17 at the concentrations of 0–60 μg ml−1 for 24 h (A) and AsPC-1 cells were treated at the concentrations of 0–230 μg ml−1 for 24 h (B). Points, percentage of living cell in three independent experiments; bars, s.d.
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fig2: The effect of PM-17 treatment on MKN45 cell and AsPC-1 cell survival in vitro. MKN45 cells were treated with PM-17 at the concentrations of 0–60 μg ml−1 for 24 h (A) and AsPC-1 cells were treated at the concentrations of 0–230 μg ml−1 for 24 h (B). Points, percentage of living cell in three independent experiments; bars, s.d.

Mentions: We examined the cytotoxic effects of PM-17 on the growth of AsPC-1 cells and MKN45 cells. These cells were suspended in RPMI 1640 culture medium containing a range of concentrations of PM-17. As shown in Figure 2, IC50 values of PM-17 against AsPC-1 cells and MKN45 cells were 175 and 40 μg ml−1, respectively.


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

Ogata A, Yanagie H, Ishikawa E, Morishita Y, Mitsui S, Yamashita A, Hasumi K, Takamoto S, Yamase T, Eriguchi M - Br. J. Cancer (2007)

The effect of PM-17 treatment on MKN45 cell and AsPC-1 cell survival in vitro. MKN45 cells were treated with PM-17 at the concentrations of 0–60 μg ml−1 for 24 h (A) and AsPC-1 cells were treated at the concentrations of 0–230 μg ml−1 for 24 h (B). Points, percentage of living cell in three independent experiments; bars, s.d.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2361451&req=5

fig2: The effect of PM-17 treatment on MKN45 cell and AsPC-1 cell survival in vitro. MKN45 cells were treated with PM-17 at the concentrations of 0–60 μg ml−1 for 24 h (A) and AsPC-1 cells were treated at the concentrations of 0–230 μg ml−1 for 24 h (B). Points, percentage of living cell in three independent experiments; bars, s.d.
Mentions: We examined the cytotoxic effects of PM-17 on the growth of AsPC-1 cells and MKN45 cells. These cells were suspended in RPMI 1640 culture medium containing a range of concentrations of PM-17. As shown in Figure 2, IC50 values of PM-17 against AsPC-1 cells and MKN45 cells were 175 and 40 μg ml−1, respectively.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Chemical Resources Laboratory, Tokyo Institute of Technology, R1-21, 4259 Nagatsuta Midori-ku Yokohama, Tokyo 226-8503, Japan.

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 [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.

Show MeSH
Related in: MedlinePlus