{BiW8 O30 } Exerts Antitumor Effect by Triggering Pyroptosis and Upregulating Reactive Oxygen Species.

We successfully synthesized {BiW8 }, a 10-nuclear heteroatom cluster modified {BiW8 O30 }. At 24 h post-incubation, the IC50 values of {BiW8 } against HUVEC, MG63, RD, Hep3B, HepG2, and MCF7 cells were 895.8, 127.3, 344.3, 455.0, 781.3, and 206.3 µM, respectively. The IC50 value of {BiW8 } on the MG63 cells was more than 2-fold lower than that of the other raw materials. Through morphological and functional features, we demonstrated pyroptosis as a newly identified mechanism of cell death induced by {BiW8 }. {BiW8 } increased 2-fold reactive oxygen species (ROS) levels in MG63 cells at 24 h post-incubation. Compared with 0 h, the glutathione (GSH) content decreased by 59, 65, 75, 94, and 97 % at 6, 12, 24, 36 and 48 h post-incubation, respectively. Furthermore, multiple antitumor mechanisms of {BiW8 } were identified via transcriptome analysis and chemical simulation, including activation of pyroptosis, suppression of GSH generation, depletion of GSH, and inhibition of DNA repair.

Inhibition of Mitochondrial ATP Synthesis and Regulation of Oxidative Stress Based on {SbW8 O30 } Determined by Single-Cell Proteomics Analysis.

The 10-nuclear heteroatom cluster modified {SbW8 O30 } was successfully synthesized and exhibited inhibitory activity (IC50 =0.29 µM). Based on proteomics analysis, Na4 Ni2 Sb2 W2 -SbW8 inhibited ATP production by affecting the expression of 16 related proteins, hindering metabolic functions in vivo and cell proliferation due to reactive oxygen species (ROS) stress. In particular, the low expression of FAD/FMN-binding redox enzymes (relative expression ratio of the experimental group to the control=0.43843) could be attributed to the redox mechanism of Na4 Ni2 Sb2 W2 -SbW8 , which was consistent with the effect of polyoxometalates (POMs) and FMN-binding proteins on ATP formation. An electrochemical study showed that Na4 Ni2 Sb2 W2 -SbW8 combined with FMN to form Na4 Ni2 Sb2 W2 -SbW8 -2FMN complex through a one-electron process of the W atoms. Na4 Ni2 Sb2 W2 -SbW8 acted as catalase and glutathione peroxidase to protect the cell from ROS stress, and the inhibition rates were 63.3 % at 1.77 µM of NADPH and 86.06 % at 10.62 µM of 2-hydroxyterephthalic acid. Overall, our results showed that POMs can be specific oxidative/antioxidant regulatory agents.

The Synthesis and Biological Function of a Novel Sandwich-Type Complex Based on {SbW9 } and Flexible bpp Ligand.

A novel sandwich-type complex [Na(H2 O)4 ][{Na3 (H2 O)5 }{Mn3 (bpp)3 } (SbW9 O33 )2 }]·8H3 O (MnSbW-bpp) (bpp = 1,3-bis(4-pyridyl) propane) is synthesized and characterized by elemental analysis, IR, thermogravimetric analysis, and single-crystal X-ray diffraction. The MnSbW-bpp compound is the first sandwich case bridged by a flexible ligand. Its biological function of MnSbW-bpp in antitumor activity is also determined in vitro and in vivo. The inhibitory proliferation and induction of apoptosis are performed by flow cytometry assay, S180 (sarcoma) tumor xenograft in ICR mice, the color Doppler ultrasound monitor, and TdT-mediated dUTP-biotin nick end labeling assay. The results show that the novel compound-MnSbW-bpp-is synthesized and identified by its physical and chemical characteristics, such as the fluorescent and paramagnetic activities. MnSbW-bpp indicates a potency inhibition of human cancer lines, such as SGC-7901, HT-29, HepG2, Hela, U2OS, SaoS2, and HMC cells. MnSbW-bpp also inhibits the growth of tumor xenograft in mice, induced cell apoptosis, and released cytochrome c in vivo and in vitro. Thus, MnSbW-bpp, as a new compound, possesses the potent inhibition of cancer cells, which indicates that the MnSbW-bpp has potential merit for the further evaluation of a novel antitumor agent.

The inhibitory effects of a new cobalt-based polyoxometalate on the growth of human cancer cells.

A new cobalt-based polyoxometalate, (Himi)2[Bi(2)W2(0)O(66)(OH)(4)Co2(H2O)(6)Na(4) (H2O)14] · 17H2O (imi = iminazole) (BWCN) has been synthesized and structurally characterized. The inhibitory activities against selected human cancer lines were also determined in this study. The cell viability and chemoresistance of BWCN on human colon carcinoma HT-29 cells were assessed by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazoliumbromide), cell morphology changes, a comet assay and western blot analysis. The typical morphologic changes of apoptosis and DNA damage indicated that BWCN could have a distinct proliferation inhibitory effect on cancer cells. BWCN as a chemotherapeutic agent also induced apoptosis on HT-29 cells and showed a significant expression of cleaved-caspase-3. These results suggested that the active site of BWCN is the polymeric anion based on the basic tectonic block {BiW(9)}, and the possible mechanism is related to the interference of DNA synthesis in cancer cells.

Novel antitumor agent, trilacunary Keggin-type tungstobismuthate, inhibits proliferation and induces apoptosis in human gastric cancer SGC-7901 cells.

A new one-dimensional chain-like compound of tungstobismuthate, [(W(OH)2)2 (Mn(H2O)3)2(Na3(H2O)14)(BiW9O33)2](Himi)2·16H2O (1) (imi = iminazole), has been synthesized in aqueous solution. The structure of 1 was identified by elemental analysis, IR, thermogravimetry (TG), X-ray photoelectron spectroscopy (XPS), (183)W-NMR, and single crystal X-ray diffraction. To investigate the inhibitory effect of 1 on human gastric adenocarcinoma SGC-7901 cells, cell proliferation and apoptosis initiation were examined by MTT assay (MTT = 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazoliumbromide), flow cytometry, nuclear staining, transmission electron microscopy, single cell gel electrophoresis, DNA fragmentation, and Western blotting. The results showed that 1 inhibited cell proliferation and induced apoptosis in SGC-7901 cells in dose-dependent manner. In addition, 1 also decreased the expression of bcl-2 protein and nuclear factor-κB p65 protein in SGC-7901 cells. And expression of bcl-2 protein exhibits a decreasing trend with increase of concentration of 1. Thus, 1 possessed a potential antitumor activity in SGC-7901 cells. This suggests that polyoxotungstates will provide a promising and novel antitumor agent in prevention and treatment of gastric adenocarcinoma.

A new molybdenum(V) nickel phosphate based on divacant [H30(Mo(V)16O32)Ni14(PO4)26O2(OH)4(H2O)8]12- wheel.

A new molybdenum nickel phosphate, [H(2)en](3)Na(4)[Ni(H(2)O)(3)][H(30)(Mo(V)(16)O(32))Ni(14)(PO(4))(26)O(2) (OH)(4)(H(2)O)(8)] x 8 H(2)O 1, has been hydrothermally synthesized and structurally characterized. Compound 1 crystallizes in the monoclinic space group P2(1)/c with a = 18.6118(6) A, b = 20.9879(6) A, c = 22.9360(5) A, beta = 116.678(2) degrees, V = 8005.5(4) A(3) and Z = 2. The polyoxoanion of 1 exhibits an unusual divacant wheel-type cluster in which two {NiO(6)} octahedra are lost from the well-known "saturated" {Mo(16)TM(16)P(26)} wheel. The two vacant sites are occupied by two protonated ethylenediamines (H(2)en) via the strong hydrogen-bonding interactions between the surface O atoms of the polyoxoanions and the amine group derived from the H(2)en ligands. DC susceptibility measurements show that compound 1 exhibits strong antiferromagnetic interactions inside the wheel-type cluster.