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ABSTRACT: A series of experimental methods including 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) test, alkaline
phosphatase (ALP) activity measurement, Oil Red O stain and measurement, mineralized function expression and quantitive real
time RT-PCR (qRT-PCR) were employed to assess the effect of Nd3+ and Sm3+ on the proliferation, differentiation and mineralization function of primary osteoblasts (OBs) in vitro at cell and molecular levels. The experimental results suggest that concentration, culture time and ion species are pivotal
factors for switching the biological effects of rare earth ions from toxicity to activity, from damage to protection, or from
down-regulation to up-regulation.
Keywordsrare earth ions-primary osteoblasts-proliferation-differentiation-adipogenic transdifferentiation-mineralization
Chinese Science Bulletin 04/2012; 55(23):2505-2511. · 1.32 Impact Factor
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ABSTRACT: The effects of Ce on the proliferation, osteogenic differentiation and mineralization function of a murine preosteoblast cell line MC3T3-E1 in vitro were investigated at cell and molecular levels. The results showed that Ce promoted the proliferation, osteogenic differentiation and mineralization function of MC3T3-E1 cells at concentrations of 0.0001, 0.001, 0.01, 0.1 and 1 μM, but turned to inhibit the proliferation, osteogenic differentiation and mineralization function at concentrations of 10, 100 and 1000 μM. Ce displayed the up-regulation of Runx2, BMP2, ALP, BSP, Col I and OCN genes at concentrations of 0.0001 and 0.1 μM; these genes were down-regulated in the MC3T3-E1 cells treated with 1000 μM Ce. The expression of BMP2, Runx2 and OCN proteins was promoted by Ce at concentrations of 0.0001 and 0.1 μM, but these proteins were down-regulated after 1000 μM Ce treatment. The results suggest that Ce likely up-regulates or down-regulates the expression of Runx2, which subsequently up- or down-regulates OB marker genes Col I and BMP2 at early stages and ALP and OCN at later stages of differentiation, thus causing to promote or inhibit the proliferation, osteogenic differentiation and mineralization function of MC3T3-E1 cells.
Biological trace element research 04/2012; 149(2):291-7. · 1.92 Impact Factor
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ABSTRACT: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide test and alkaline phosphatase activity assay were employed to assess the effects of mixed trace elements including Zn(2+), Ca(2+), and Mn(2+) plus total flavonoids or icariin from Epimedium koreanum on the proliferation and differentiation of primary osteoblasts in vitro. The results indicated that icariin (0.1, 1, and 10 μmol/L) and total flavonoids (0.06, 0.6, and 6 μg/mL) inhibited the proliferation and promoted the differentiation of primary osteoblasts. Mixed trace elements including Zn(2+), Ca(2+), and Mn(2+) (0.1, 1, and 10 μmol/L) inhibited the proliferation and promoted the differentiation at 0.1 and 1 μmol/L, but inhibited the differentiation at 10 μmol/L. The effects of mixed trace elements including Zn(2+), Ca(2+), and Mn(2+) plus total flavonoids or icariin from E. koreanum on the proliferation and differentiation of primary osteoblasts in vitro are complicated, and both synergistic and antagonistic effects are generated. The results suggest that there may be a potential cooperative action between flavonoids and trace metal elements on the proliferation and differentiation of primary osteoblasts by forming metal complexes. The combination model between flavonoids and trace metal elements is a pivotal factor for switching the biological effects from toxicity to activity, from damage to protection.
Biological trace element research 02/2011; 143(3):1746-57. · 1.92 Impact Factor
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ABSTRACT: Cisplatin has become one of the most commonly used compounds for the treatment of a wide spectrum of human malignancies. Unfortunately, cisplatin has several major drawbacks. Driven by the impressive impact of cisplatin on cancer chemotherapy, great efforts have been made to develop new derivatives with improved pharmacological properties. Among the over 30 platinum agents which have entered clinical trials after the onset of clinical studies with cisplatin in the early 1970s, only carboplatin and oxaliplatin have received worldwide approval so far, nedaplatin, lobaplatin and heptaplatin have gained regionally limited approval. It has become quite evident that mere analogues of cisplatin or carboplatin will not probably offer any substantial clinical advantages over the existing drugs. Consequently, attention turned to the synthesis of non-classical platinum anticancer drugs which were capable of forming a different range of DNA adducts which could display a different spectrum of anticancer activity compared to cisplatin. The status of non-classical bi- and multi-nuclear platinum anticancer drug development has been reviewed. This review will summarize the structural types and structure-activity of non-classical mononuclear platinum anticancer drugs, and discuss their future potential as anticancer agents.
Mini Reviews in Medicinal Chemistry 10/2009; 9(11):1357-66. · 2.53 Impact Factor
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ABSTRACT: Six new type binuclear platinum(II) complexes (a-f) have been synthesized and characterized by elemental analysis, conductivity, thermal analysis, IR, UV, (1)H NMR and mass spectra techniques. The cytotoxicity of the complexes was tested by MTT and SRB assays. The cell cycle analysis and the levels of total platinum bound to DNA were measured by flow cytometry and ICP-MS, respectively. The results indicate that the complex (a) has no cytotoxicity against HL-60, BGC-823, Bel-7402, KB and Hela, the complexes (b, c, e and f) have weaker cytotoxicity against some tested carcinoma cell lines, the complex (d) has better cytotoxicity against HL-60, BGC-823, Bel-7402, KB, MCF-7, HCT-8 and Hela with respect to the IC(50) values obtained. The cytotoxicity of the complex (d) is equal to that of cisplatin against HL-60 and Bel-7402 (P>0.05), but it has better cytotoxicity than that of cisplatin against BGC-823 and MCF-7 (P<0.05). The complex (d) causes significant G(2)/M arrest and a concomitant decrease of cell population in G(1) and S phases, and the total DNA platination levels of the complex (d) are higher than those of cisplatin under the same experimental conditions. It suggests that the bridging linker has important effect on their cytotoxicity. Indeed, when the bridging linker is dicarboxylic acid, their cytotoxicity is better than that of platinum complexes with an amino acid as bridging linker. The new type binuclear platinum(II) complexes represent a novel class of anticancer agents, which deserves further attention in search of anticancer lead compounds.
European journal of medicinal chemistry 07/2009; 44(11):4772-7. · 3.27 Impact Factor
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ABSTRACT: Six new mixed ammine/ethylamine platinum(II) complexes with carboxylates [Pt(II)(NH(3))(C(2)H(5)NH(2))X(2)] (a-f) (X = CH(3)COO(-), CH(2)ClCOO(-), C(6)H(5)-COO(-), p-CH(3)-C(6)H(4)-COO(-), p-CH(3)O-C(6)H(4)-COO(-), p-NO(2)-C(6)H(4)-COO(-)) (a-f) have been synthesized and characterized by elemental analysis, conductivity, spectra techniques (IR, UV and (1)H NMR). The cytotoxicity of the complexes was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The relative reactivity of leaving groups of complex (c) with G-actin was determined spectrophotometrically at 412 nm. The results show that the complexes (a-f) confer substantially greater cytotoxicity against EJ and HL-60 than the other carcinoma cell lines, moreover, the cytotoxicity of complexes (c-e) is equal to that of cisplatin against HL-60, and the cytotoxicity of complex (c) is also equal to that of cisplatin against EJ. However the complexes (a-f) are significantly less potent than cisplatin against BGC-823, HCT-8 and MCF-7. The reactivity of leaving groups decreases in the sequence: cisplatin>c>carboplatin. The results suggest that ammine/ethylamine platinum(II) complexes with carboxylate anion as leaving group have selectivity against carcinoma cell lines. When leaving group is aromatic carboxylate ion, the complexes have better cytotoxicity, moreover, the substitution radical in benzene ring also influences cytotoxicity.
European journal of medicinal chemistry 12/2008; 44(6):2758-62. · 3.27 Impact Factor
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ABSTRACT: A series of experimental methods including 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) test, alkaline phosphatase (ALP) activity measurement, oil red O stain and measurement, mineralized function and quantitive real time RT-PCR (qRT-PCR) were employed to assess the effects of Er3+ on the proliferation, differentiation and mineralization function of primary osteoblasts (OBs) in vitro at cell and molecular levels. The results indicated that Er3+ inhibited the proliferation of OBs at a concentration of 1×10−7 mol/L, but had no effect at other concentrations. Er3+ inhibited the differentiation of OBs at concentrations of 1×10−8, 1×10−7, and 1×10−6 mol/L, but had no effect at a higher concentration of 1×10−5 mol/L. Er3+ had no effect on the transdifferentiation of OBs at tested concentrations. Er3+ inhibited the mineralization function of OBs at concentrations of 1×10−7, 1×10−6, and 1×10−5 mol/L, but had no effect at a lower concentration of 1×10−8 mol/L. The expression of the mRNA for runt-related transcription factor 2 (RUNX-2) and peroxisome proliferators activated receptor γ (PPAR-γ) was down-regulated in the presence of 1×10−6 mol/L Er3+. These findings suggested that Er3+ might have negative effect on bone metabolism.
Journal of Rare Earths 29(5):507-510. · 0.90 Impact Factor
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ABSTRACT: The effects of cerium ion (Ce3+) on the proliferation, differentiation, adipocytic transdifferentiation and mineralization function of primary mouse osteoblasts (OBs) were investigated. The results indicated that Ce3+ at all concentrations (1 × 10−9, 1 × 10−8, 1 × 10−7, 1 × 10−6, 1 × 10−5, and 1 × 10−4 mol/L) promoted the proliferation of osteoblasts (OBs). On day 1 and 3, Ce3+ promoted the differentiation of OBs at concentrations of 1 × 10−9, 1 × 10−7, and 1 × 10−6 mol/L, but inhibited the differentiation of OBs at higher concentrations. On day 2, Ce3+ inhibited the differentiation of OBs at tested concentrations. On day 9 and 12, Ce3+ inhibited the adipocytic transdifferentiation of OBs at most concentrations. On day 15, Ce3+ promoted the adipocytic transdifferentiation of OBs at concentrations of 1 × 10−9, 1 × 10−6, 1 × 10−5, and 1 × 10−4 mol/L, but had no effects at other concentrations. Ce3+ inhibited the formation of mineralized matrix nodules of OBs at concentrations of 1 × 10−9, 1 × 10−8 and 1 × 10−7 mol/L, and promoted the formation of mineralized matrix nodules of OBs at other concentrations. These findings suggested that the effects of Ce3+ on the proliferation, differentiation, adipocytic transdifferentiation and mineralization function of primary OBs depended on the concentration and culture time; moreover, they were pivotal factors for switching the biological effects of Ce3+ from toxicity to activity, from damage to protection, or from down-regulation to up-regulation.
Journal of Rare Earths.
