Shuxiang Wang

Cerium oxide nanoparticles protect endothelial cells from apoptosis induced by oxidative stress.

Oxidative stress is well documented to cause injury to endothelial cells (ECs), which in turn trigger cardiovascular diseases. Previous studies revealed that cerium oxide nanoparticles (nanoceria) had antioxidant property, but the protective effect of nanoceria on ROS injury to ECs and cardiovascular diseases has not been reported. In the current study, we investigated the protective effect and underlying mechanisms of nanoceria on oxidative injury to ECs. The cell viability, lactate dehydrogenase release, cellular uptake, intracellular localization and reactive oxygen species (ROS) levels, endocytosis mechanism, cell apoptosis, and mitochondrial membrane potential were performed. The results indicated that nanoceria had no cytotoxicity on ECs but had the ability to prevent injury by H2O2. Nanoceria could be uptaken into ECs through caveolae- and clathrin-mediated endocytosis and distributed throughout the cytoplasma. The internalized nanoceria effectively attenuated ROS overproduction induced by H2O2. Apoptosis was also alleviated greatly by nanoceria pretreatment. These results may be helpful for more rational application of nanoceria in biomedical fields in the future.

Synthesis, characterization, and cytotoxicity of complexes of platinum(II) with 2,2′-bipyridine and N-benzoyl-L-amino acid dianion

Four new platinum(II) complexes (1–4) with N-benzoyl-L-amino acid and bipy were synthesized and characterized by elemental analysis, IR, UV, 1H NMR, and mass spectra. The crystal structure of 1 was determined by X-ray diffraction analysis. Cytotoxicities were measured by MTT and SRB assays. Complexes 1–4 exert cytotoxicity with selectivity against HL-60, Bel-7402, BGC-823, and KB cell lines. This suggests that amino acids and acylated groups have important effects on cytotoxicity; the cytotoxicity is also related to the species of tumor cells, but the IC50 values do not show definite correlation with the variation of amino acids and acylated groups.

Synthesis, characterization and cytotoxicity of platinum(II)/palladium(II) complexes with 1,3-diaminopropane and 4-toluensulfonyl-L-amino acid dianion.

Eight novel platinum(II)/palladium(II) complexes with 1,3-dap and 4-toluensulfonyl-l-amino acid dianion, [Pt(1,3-dap)(TsalaNO)]·0.5H(2)O (1a), [Pt(1,3-dap)(TsvalNO)] (1b), [Pt(1,3-dap)(TspheNO)] (1c), [Pt(1,3-dap)(TsserNO)] (1d), [Pd(1,3-dap)(TsalaNO)]·1.5H(2)O (2a), [Pd(1,3-dap)(TsvalNO)] (2b), [Pd(1,3-dap)(TspheNO)] (2c) and [Pd(1,3-dap)(TsileNO)] (2d) have been synthesized and characterized by elemental analysis, IR, UV, (1)H NMR and mass spectrometry techniques. Crystal structure of the complex 1b has been determined by X-ray diffraction. The cytotoxicity was tested by MTT and SRB assays. The complexes (1a-1d and 2a-2d) exert cytotoxicity against Bel-7402, HL-60, KB and BGC-823, but none of them is more active than cisplatin. The results suggest that metal ions, amino acids and aliphatic N-containing ligands have effect on cytotoxicity, while the IC(50) values do not show definite correlation with variation of them.

Synthesis, anticancer activity and DNA-binding properties of novel 4-pyrazolyl-1,8-naphthalimide derivatives.

A novel series of 4-pyrazolyl-1,8-naphthalimide derivatives have been designed and facilely synthesized. For anticancer activity in vitro, most of the compounds were found to be more toxic against human mammary cancer cells (MCF-7) than human cervical carcinoma cells (Hela) and human lung cancer cells (A549). Compounds 4i, 4h, 4b and 4a showed improved cytotoxic activity against MCF-7 cells over amonafide, in particular compounds 4i and 4h, the IC50 values of which against cell lines of MCF-7 were 0.51 μM and 0.79 μM, respectively. The DNA-binding properties of 4i were investigated by UV-vis, fluorescence, and Circular Dichroism (CD) spectroscopies and thermal denaturation. The results indicated that compound 4i as the DNA-intercalating agent exhibited middle binding affinity with CT-DNA.

Synthesis, characterization, and cytotoxicity of platinum(II)/palladium(II) complexes with 4-toluenesulfonyl-L-amino acid dianion and diimine/diamine

Eight new platinum(II)/palladium(II) complexes with 4-toluenesulfonyl-L-amino acid dianion and diimine/diamine ligands, [Pd(en)(Tsile)]·H2O (1), [Pd(bipy)(Tsile)] (2), [Pd(bipy)(Tsthr)]·0.5H2O (3), [Pd(phen)(Tsile)]·0.5H2O (4), [Pd(phen)(Tsthr)]·H2O (5), [Pd(bqu)(Tsthr)]·1.5H2O (6), [Pt(en)(Tsser)] (7), and [Pt(en)(Tsphe)]·H2O (8), have been synthesized and characterized by elemental analyses, 1H NMR and mass spectrometry. The crystal structure of 7 has been determined by X-ray diffraction. Cytotoxicities were tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and sulforhodamine B assays. The complexes exert cytotoxicity against HL-60, Bel-7402, BGC-823, and KB cell lines with 4 having the best cytotoxicity against HL-60, Bel-7402, and BGC-823 cell lines; the compounds are less cytotoxic than cisplatin.

Effects of La3+ on osteogenic and adipogenic differentiation of primary mouse bone marrow stromal cells

Abstract In order to elucidate the action of La 3+ on bone metabolism, effects of La 3+ on the osteogenic and adipogenic differentiation of primary mouse bone marrow stromal cells (BMSCs) were studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test, alkaline phosphatase (ALP) activity measurement, mineralized function, oil red O stain and measurement. The results showed that La 3+ promoted the proliferation of BMSCs except at 1×10 −10 and 1×10 −6 mol/L. The effect of La 3+ on the osteogenic differentiation depended on concentrations at the 7th day, but the osteogenic differentiation was inhibited at any concentration at the 14th day. La 3+ promoted the formation of mineralized matrix nodules except at 1×10 −8 and 1×10 −5 mol/L. La 3+ inhibited adipogenic differentiation except at 1×10 −10 and 1×10 −7 mol/L at the 10th day, and inhibited adipogenic differentiation except at 1×10 −9 mol/L at the 16th day. These findings suggested that La 3+ might have protective effect on bone at appropriate dose and time. This would be valuable for better understanding the mechanism of the effect of La 3+ on bone metabolism.

Defect-Related Luminescent Hydroxyapatite-Enhanced Osteogenic Differentiation of Bone Mesenchymal Stem Cells Via an ATP-Induced cAMP/PKA Pathway

Novel defect-related hydroxyapatite (DHAP), which combines the advantages of HAP and defect-related luminescence, has the potential application in tissue engineering and biomedical area, because of its excellent capability of monitoring the osteogenic differentiation and material biodegradation. Although the extracellular mechanism of DHAP minerals and PO4(3-) functioning in osteogenic differentiation has been widely studied, the intracellular molecular mechanism through which PO4(3-) mediates osteogenesis of bone mesenchymal stem cells (BMSCs) is not clear. We examined a previously unknown molecular mechanism through which PO4(3-) promoted osteogenesis of BMSCs with an emphasis on adenosine-triphosphate (ATP)-induced cAMP/PKA pathway. Our studies showed that DHAP could be uptaken into lysosome, in which PO4(3-) was released from DHAP, because of the acid environment of lysosome. The released PO4(3-) interacted with ADP to form ATP, and then degraded into adenosine, an ATP metabolite, which interacted with A2b adenosine receptor to activate the cAMP/PKA pathway, resulting in the high expression of osteogenesis-related genes, such as Runx2, BMP-2, and OCN. These findings first revealed the function of ATP-metabolism in bone physiological homeostasis, which may be developed to cure bone metabolic diseases.

Design, synthesis, and biologic evaluation of some novel N-arylpyrazole derivatives as cytotoxic agents

A novel series of N-arylpyrazole derivatives (5a–5d, 7a–7c) has been designed and synthesized via aromatic substitution reaction of N-nonsubstituted pyrazoles with 4-fluoronitrobenzene in the presence of base. The structures of these compounds were established on the basis of elemental (C, H, and N) and spectral analysis (1H NMR, 13C NMR, HRMS, and FT-IR). All the compounds were tested for their cytotoxic activity in vitro against four human tumor cell lines: carcinoma (Bel-7402), nasopharyngeal carcinoma (KB), immature granulocyte leukemia (HL-60), and gastrocarcinoma (BGC-823) by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The results showed that most of the obtained compounds exhibited promising cytotoxicity against tested carcinoma cell lines with low IC50 values. The bis-pyrazole derivative 7c, bearing alkoxy group on the 5-position of phenyl ring, was the most effective one. It is inhibition of cell growth of Bel-7402 cells was 1.5-fold higher than that found for cisplatin. And, also mono-pyrazole derivatives 5a and 5b, decorated with trifluoromethyl group on the phenyl ring, displayed better cytotoxicity than that of cisplatin against Bel-7402 cell line.

Synthesis, characterization, and cytotoxicity of complexes of palladium(II) with 1,4-diaminobutane/1,3-diaminopropane and 4-toluenesulfonyl-L-amino acid dianion

Eight new palladium(II) complexes with 4-toluenesulfonyl-L-amino acid dianion and 1,4-dab/1,3-dap, [Pd(1,4-dab)(TsglyNO)] · H2O (1), [Pd(1,4-dab)(TsvalNO)] (2), [Pd(1,4-dab)(TsleuNO)] (3), [Pd(1,4-dab)(TsileNO)] (4), [Pd(1,4-dab)(TsserNO)] · 0.5H2O (5), [Pd(1,4-dab)(TspheNO)] · 0.5H2O (6), [Pd(1,4-dab)(TsthrNO)] · H2O (7), and [Pd(1,3-dap)(TsserNO)] (8), have been synthesized and characterized by elemental analysis, IR, UV, 1H NMR, and mass spectrometry. Crystal structure of 8 has been determined by X-ray diffraction. The cytotoxicities were tested by MTT assay. The results indicate the complexes exert cytotoxic effects against HL-60 and Bel-7402. The structure–activity relationship suggests that both amino acids and N-containing ligands have important effects on cytotoxicity, but the IC50 values do not show definite correlation with variation of these ligands.

Synthesis, cytotoxicity, and DNA-binding property of berberine derivatives

Abstract 9-Substituted berberine derivatives (4a–4f) with polyethylene glycol side chain and terminal group were synthesized and characterized by elemental (C, H, and N) and spectral analysis (NMR, HRMS and FTIR). These compounds were tested for their in vitro cytotoxic activity against four human tumor cell lines: granulocyte leukemia (HL-60), gastrocarcinoma (BGC-823), carcinoma (Bel-7402), and nasopharyngeal carcinoma (KB) by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The DNA-binding properties were investigated by UV–Vis absorption, fluorescence, CD spectroscopies, and thermal denaturation measurements. The results indicated that 4a–4f exerted cytotoxic effects with selectivity against tested cell lines. 4a exhibited higher cytotoxicity than cisplatin, berberine, and berberrubine against HL-60 and BGC-823 cell lines. The length of side chains and nature of terminal groups played an important role in the cytotoxicity. Berberine derivatives binded to CT-DNA in an intercalating mode. The binding affinities decreased with the increasing length of side chains. Compounds 4a–4c and 4e could change the DNA conformation from B to A-like form.