Biomedical subjects

Jian Ding

Publications and source records attributed to Jian Ding.

At least 91 records · Page 5Linked to original sources

PubMed2004

Evaluation of active recombinant catalytic domain of human ErbB-2 tyrosine kinase, and suppression of activity by a naturally derived inhibitor, ZH-4B.

Human cancers frequently express high levels of ErbB-2 tyrosine kinase, which is associated with aggressive tumor behavior and poor prognosis. ErbB-2 is thus a promising target for cancer therapy. Here we express the catalytic domain of ErbB-2 as a soluble active kinase, and investigate the correlations between its activity and kinase concentration, ATP concentration, substrate concentration and divalent cation type. A simple and effective screening model is established to identify and evaluate potential inhibitors of ErbB-2 kinase. ZH-4B, a naturally derived small molecule compound that potently inhibits ErbB-2 kinase activity with an IC50 value of 2.45+/-0.56 microM, is identified. In SK-OV-3 human ovarian cancer cells and SK-BR-3 human breast carcinoma cells, ZH-4B blocks epidermal growth factor (EGF)-induced phosphorylation of ErbB-2 in a dose-dependent manner. Our data collectively indicate that ZH-4B is a potential novel anti-cancer agent that deserves further investigation.

Animals↗

PubMed2004

Synthesis and biological evaluation of bis and monocarbonate prodrugs of 10-hydroxycamptothecins.

In an effort to improve the stability of labile lactone ring of camptothecins, the bis and mono-alkyl carbonate prodrugs of 10-hydroxycamptothecins were synthesized and their chemical and enzymatical stability as well as antitumor activity were studied. The in vitro evaluation of the stability of these carbonates indicates that the 10,20-biscarbonates are firstly hydrolyzed to afford the stable 20-monocarbonates. And the 10-carbonates are not stable in human plasma, mouse plasma and pH7.4 phosphate buffer, while the 20-carbonates are relatively stable in the three media and can be readily cleaved by porcine liver esterase. The overall toxicity of the tested carbonate against mice bearing S180 sarcoma is much lower when compared with the parent compound, and the antitumor activity is maintained.

Animals↗

PubMed2004

ERbeta exerts multiple stimulative effects on human breast carcinoma cells.

Recent studies of ERs in breast cancer have demonstrated the existence of ERbeta in addition to ERalpha. Some clinical data indicated that ERbeta had prognostic value for patient's survival, which suggested that ERbeta plays a key role in breast cancer development and metastasis. To test this hypothesis, we generated an ERbeta high-expression cell line by reintroduced human ERbeta cDNA into MDA-MB-435 cells. We demonstrated that ERbeta exerted multiple tumor-stimulative effects on human breast carcinoma cells both in vivo and in vitro. In in vitro studies, ERbeta was able to increase the proliferation and invasion of MDA-MB-435 cells significantly, while these effects were totally estradiol independent. Also, this stimulation was characterized by downregulation of p21 and upregulation of MMP-9, as well as transcriptional factor Est-1. In in vivo studies, we also demonstrated that ERbeta-transfected MDA-MB-435 cells grew much faster and had more pulmonary metastasis than mock or wild-type cells in nude mice. In ERbeta-transfected MDA-MB-435 xenografts, ERbeta caused significant reduction in p21 protein levels. Similar effects of ERbeta on MMP-9 and Ets-1 expression noted in vitro studies were also observed in the in vivo studies. These in vitro and in vivo studies indicated that ERbeta exerted multiple stimulative effects on breast cancer development and metastasis.

Animals↗

PubMed2004

Characterization of salvicine-resistant lung adenocarcinoma A549/SAL cell line.

Salvicine is a diterpenoid quinone derived from a traditional Chinese medication that has been shown to possess potent in vitro and in vivo antitumor effects. This compound, which inhibits the activity of Topoisomerase II, was found to equipotently kill various multidrug-resistant tumor cells and their corresponding parental counterparts in vitro and to inhibit mdr1/P-gp expression in multidrug-resistant K562/A02 cells. To examine the features of tumor resistance to salvicine, we established a salvicine-resistant tumor cell subline of A549 lung adenocarcinoma cells. Compared with parental cells, A549/SAL cells displayed 8.91-fold resistance to salvicine and an average of 6.70-fold resistance to the antimetabolites. A549/SAL cells, however, were not resistant to alkylating agents, platinum compounds and other naturally-derived antineoplastics. RT-PCR analysis showed that the expression of mRNAs from the mdr-1, MRP, PCNA, topoisomerase II alpha and beta, GSTpi, p21 and GADD45 genes was not altered in the salvicine-resistant subline. In contrast, expression of p53 and bax mRNA was significantly lower, and expression of mdm2 mRNA was significantly higher, in A549/SAL cells compared to A549 cells. A549/SAL cells grew more slowly, and in a more scattered pattern, than A549 cells. In addition, the A549/SAL cells showed enhanced ability to migrate and invade in comparison to the parental cells. These results indicate that exposure to salvicine does not induce a tumor multidrug-resistant phenotype.

Antineoplastic Agents↗

PubMed2004

Anti-angiogenic effects of Shiraiachrome A, a compound isolated from a Chinese folk medicine used to treat rheumatoid arthritis.

The Chinese folk medicine Shiraia bambusicola has long been utilized in the treatment of rheumatoid arthritis, a disease in which angiogenesis plays an important role. We report here the isolation of the compound Shiraiachrome A from S. bambusicola and the demonstration of its anti-angiogenic properties. We found that Shiraiachrome A significantly inhibited the proliferation, migration, and tube formation of human microvascular endothelial cells (HMEC) in a dose-dependent manner, with average IC(50) values of 2.1+/-0.36, 1.97+/-0.44, and 1.65+/-0.59 microM, respectively. In addition, Shiraiachrome A inhibited the formation of new microvessels in a rat aorta culture model as well as in the chick embryo chorioallantoic membrane (CAM) assay. Investigation of the mechanism of action of Shiraiachrome A demonstrated that this compound suppressed the autophosphorylation of four receptor tyrosine kinases (RTKs), with IC(50) values ranging from 2.2 to 4.3 microM. These results suggest that Shiraiachrome A inhibits angiogenesis by blocking growth factor-stimulated autophosphorylation of RTKs. These findings also indicate that Shiraiachrome A may be a potent therapeutic agent for angiogenesis-related diseases such as cancer, rheumatoid arthritis, and diabetic retinopathy.

Angiogenesis Inhibitors↗

PubMed2004

Lingshuiol, a novel polyhydroxyl compound with strongly cytotoxic activity from the marine dinoflagellate Amphidinium sp.

A novel polyhydroxy compound with a linear carbon-chain, lingshuiol (1), had been isolated from the cultured marine dinoflagellate Amphidinium sp. Its structure was elucidated by extensive analysis of 2D NMR spectral data. Lingshuiol possessed a powerful cytotoxic activity against A-549 and HL-60 cells in vitro with the IC(50) of 0.21 and 0.23 microM, respectively.

Alkenes↗

PubMed2004

A novel cytotoxic ternary copper(II) complex of 1,10-phenanthroline and L-threonine with DNA nuclease activity.

A novel ternary copper(II) complex, [Cu(phen)(L-Thr)(H2O)](ClO4) (phen=1,10-phenanthroline, L-Thr=L-threonine), has been synthesized and structurally characterized. The complex crystallized in a triclinic system with space group P1 , a=7.526(15) A, b=11.651(2) A, c=12.127(2) A, alpha=115.41(3) degrees , beta=102.34(3) degrees and gamma=91.33(3) degrees . The copper(II) center is situated in a distorted square-pyramidal geometry. At a concentration of 10(-6) mol L(-1), the complex exhibited potent cytotoxic effects against human leukemia cell line HL-60 and human stomach cancer cell line SGC-7901 with inhibition rates of over 90%, however, less pronounced effects were observed for human liver carcinoma cell line BEL-7402 and human non-small-cell lung cancer cell line A-549. The complex was shown to bind DNA by intercalation and cleave pBR322 DNA in the presence of ascorbate.

Ascorbic Acid↗

PubMed2004

Cytotoxic sesquiterpene lactones from Eupatorium lindleyanum.

Ten new guaiane type sesquiterpene lactones, namely, eupalinilides A-J (1-10), as well as nine known compounds, eupachinilide C (11), eupachifolin D (12), eupachinilide E (13), 2alpha-hydroxyeupatolide (14), 3-deacetyleupalinin A (15), heliangine (16), 8beta-tigloyloxy-2,3-seco-6betaH,7alphaH-helianga-4Z,11(13)-diene-3,10beta;6, 12-diolid-2-oic acid (17), 8beta-(4'-hydroxytigloyloxy)-3beta,14-dihydroxy-6betaH,7alphaH-germacra-1(10)Z,4Z,11(13)-trien-6,12-olide (18), and 8beta-tigloyloxy-3beta,14-dihydroxy-6betaH,7alphaH-germacra-1(10)Z,4E,11(13)-trien-6,12-olide (19), were isolated from the whole plant of Eupatorium lindleyanum. Eupalinilides B (2), C (3), E (5), F (6), and I (9) have been tested for cytotoxicity against P-388 and A-549 tumor cell lines. The results showed that eupalinilides B (2) and E (5) demonstrated potent cytotoxicity. The structures of these compounds were determined by spectroscopic methods including 1D and 2D NMR spectra.

Animals↗

PubMed2004

Anticancer activity of methoxymorpholinyl doxorubicin (PNU 152243) on human hepatocellular carcinoma.

Methoxymorpholinyl doxorubicin (PNU 152243) is a morpholinyl analog possessing a methoxymorpholinyl group at the 3' position of the sugar moiety, which, compared with doxorubicin, appears to be less cardiotoxic and more cytotoxic against multidrug-resistant tumor cells. In this study, we report the anticancer activity of PNU 152243 on human hepatocellular carcinoma (HCC) in vitro and in vivo. The average IC50 value of PNU was 0.08 microM. In contrast, the average IC50 values of adriamycin (ADM), 4'-epidoxorubicin (EDR), mitomycin C (MMC), cisplatin and vepesid (VP-16) were 0.96, 0.74, 2.81, 7.27 and 26.66 microM, respectively. PNU 152243 was 13.7, 10.6, 40.1, 103.8 and 380.8 times more potent than ADM, EDR, MMC, cisplatin and VP-16 against HCC in vitro. In nude mice, the T/C (%) were 43.8 at the dose of 25 microg/kg and 41.2 at the dose of 50 microg/kg on BEL-7402 xenograft, the T/C (%) were 41.7 at the dose of 25 microg/kg and 54.6 at the dose of 50 microg/kg on Zip-177 xenograft. The results showed that PNU 152243 had growth inhibition of HCC in vitro and in vivo and may be useful in HCC chemotherapy.

Animals↗

PubMed2004

Immunogenic comparison of two coupling methods of marine polysaccharide to bovine serum albumin.

Two conjugates of marine polysaccharide (MPS) and bovine serum albumin (BSA) were prepared using two methods, periodate oxidation and reductive amination, with the intent of enhancing its immunogenicity. Sera samples from Balb/c mice immunized with the products named MPS-BSAp and MPS-BSAr respectively were evaluated by enzyme-linked-immunosorbent assay (ELISA). The results showed that mice immunized with MPS-BSAp produced antibodies not against MPS but rather against MPS-BSAp, while the mice immunized with MPS-BSAr produced high titer antibodies only specific for MPS. The difference was attributed to the fact that the epitopes of MPS had been changed in the coupling process by periodate oxidation. A mouse immunized with MPS-BSAr was chosen to prepare monoclonal antibodies (mAbs) specific for polysaccharide MPS. A hybridoma cell line that secreted monoclonal antibody recognizing specifically polysaccharide MPS was established.

Animals↗

PubMed2004

Acidic oligosaccharide sugar chain, a marine-derived acidic oligosaccharide, inhibits the cytotoxicity and aggregation of amyloid beta protein.

In this paper, we investigated interactions of the acidic oligosaccharide sugar chain (AOSC), derived from brown algae Echlonia kurome OKAM, with amyloid beta protein (Abeta). We observed that AOSC inhibited the toxicity induced by Abeta in both primarily cortical cells and the SH-SY5Y cell line. We also observed that AOSC inhibited the apoptosis induced by Abeta in SH-SY5Y by reducing the elevated level of intracellular calcium concentration ([Ca(2+)](i)) and suppressing the generation of reactive oxygen species. Surface plasmon resonance analysis demonstrated that AOSC had affinity for both freshly-dissolved Abeta and 48-h incubated Abeta. Furthermore, AOSC blocked the fibril formation of Abeta, which may be responsible for its anti-cytotoxic effects. Thus, our results indicate that AOSC might be a potentially therapeutic compound for Alzheimer's disease.

Amyloid beta-Peptides↗

PubMed2004

[Heat shock protein 90: novel target for cancer therapy].

The molecular chaperone heat shock protein 90 (Hsp90) is important in maintaining the conformation, stability, and function of many proteins involved in cell surviving. Hsp90 is of interest as an anticancer drug target because of its importance in maintaining the function of key oncogenic client proteins. Hsp90 inhibitors also have shown promising antitumor activity in vitro and in vivo preclinical model systems. One Hsp90 inhibitor, 17-allylamio-17- desmethoxygeldanamycin (17-AAG), is currently in clinical trial.

Animals↗

PubMed2004

Losartan inhibited expression of matrix metalloproteinases in rat atherosclerotic lesions and angiotensin II-stimulated macrophages.

AIM: To explore whether the angiotensin II (Ang II) receptor 1 (AT1) antagonist, losartan could reduce activity and expression of matrix metalloproteinases (MMPs) in rat atherosclerotic plaques. METHODS: Male Wistar-Kyoto rats were ip injected a single dose of vitamin D3 600 kU x kg(-1) x month(-1) and fed an atherogenic diet for 4 months to induce experimental atheroma. Then either placebo or losartan 50 mg x kg(-1) x d(-1) was administered in rats for another 2 months. In vitro, the effect of losartan 0.1-10 micromol/L on the expression of MMP-2 and MMP-9 was investigated in Ang II-stimulated rat peritoneal macrophages. The expression and activity of MMP-2 and MMP-9 were monitored by Western blot, RT-PCR, and SDS-PAGE zymography analysis. RESULTS: High levels of MMP-2 and MMP-9 were expressed in rat atherosclerotic lesions. Losartan significantly reduced the activity and expression of MMP-2 and MMP-9 compared with the placebo group (MMP-2, 5861+/-539 vs 8991+/-965, P<0.05; MMP-9,10527+/-1002 vs 14623+/-2462, P<0.01). In cultured rat peritoneal macrophages, Ang II 0.1 micromol/L elicited an increase in MMP-2 and MMP-9 activity and expression that were prevented by losartan in a dose-dependent manner (P<0.01). But the AT2 receptor antagonist PD123319 had no effect. CONCLUSION: Losartan reduced the expression and activity of MMP-2 and MMP-9 in rat atherosclerotic lesions. The anti-atherogenic effects of losartan were due to the direct inhibition of Ang II bioactivity.

Angiotensin II↗

PubMed2004

[Risk factors for allergic asthma in a case-control study among adults].

OBJECTIVE: To investigate the risk factors allergic asthma in adult as well as the indoor environmental risk factors. METHODS: Case-control study was used to collect the information from 102 cases of adults' allergic asthma and 394 controls. The information included general social demographic characteristics, disease history, smoking history, occupation, indoor environmental situation and genetic history of the families. RESULTS: The case group had higher proportion of the history on occupational dust exposure than the control group (P < 0.05, OR = 1.78) with statistical significance. Poorer housing condition were more likely to cause adult allergic asthma or onset, with an odds ratio of 3.24. The results also showed that there was a correlation between the frequency of "quilt solarization" and adult allergic asthma (P < 0.10, OR = 1.53). We also found that the frequency of having woody floor in the living room of the patients cases was higher than that in the controls (P < 0.01, OR = 2.33) so as the degree of indoor cooking-oil fume contamination (P < 0.01, OR = 2.52). The statistical significant correlation was also found between the adult allergic asthma and the history of asthma or chronic bronchitis of their parents (P < 0.01, OR = 2.32). CONCLUSIONS: The study showed that the indoor environmental risk factors as poor housing condition, fewer frequency of solarization for quilts, woody floor in the living room as well as indoor cooking-oil fume contamination were the possible risk factors related to adult allergic asthma. Occupational dust exposure and the family genetic history were also the possible risk factors. The study indicated that adult allergic asthma was a multi-factorial complex disease and the interaction of environmental and genetic risk factors played an important role in the onset of this disease.

Adult↗

PubMed2004

[The emergent role of p38 MAPKs in the regulation of cell cycle].

The p38 MAPKs are members of the MAPK family. Its pathway has been traditionally associated with the stress and immune response. More recently, it has been reported that the p38 MAPKs pathway can also regulate apoptosis and some differentiation process. It can regulate cellular growth and cell cycle checkpoints in different ways depending on the cell type and the stimulus.

Animals↗

PubMed2003

Cytotoxicity, apoptosis induction and downregulation of MDR-1 expression by the anti-topoisomerase II agent, salvicine, in multidrug-resistant tumor cells.

Salvicine, a novel topoisomerase II inhibitor and a diterpenoid quinone compound, exerts potent in vitro and in vivo antitumor effects. In our study, we show that salvicine effectively kills multidrug-resistant (MDR) sublines, such as K562/A02, KB/VCR and MCF-7/ADR, and parental K562, KB and MCF-7 cell lines to an equivalent degree. These cytotoxic activities of salvicine were much more potent than those of several classical anticancer drugs (average resistance factor: 1.42 for salvicine vs. 344.35, 233.19 and 71.22 for vincristine, doxorubicin and etoposide, respectively). Flow cytometry and DNA agarose gel electrophoresis demonstrated that salvicine induced similar levels of apoptosis in MDR K562/A02 and parental cells. The compound activated caspase-1 and -3 (but not caspase-8) and increased the ratio of bax to bcl-2 mRNA via reduction of bcl-2 mRNA expression in the same cells. Furthermore, salvicine induced the downregulation of mdr-1 gene and P-gp expression but had no effect on MRP and LRP gene expression in MDR K562/A02 cells. These results suggest that the reduction of mdr-1 and bcl-2 expression by salvicine possibly contributes to its cytotoxicity and apoptotic induction in this system. The effectiveness, broad-spectrum activity and possibly novel mechanism of killing MDR tumor cells in vitro of salvicine signify promising in vivo and clinical activity. The novel chemical structure of this compound further implies a role for salvicine in future MDR tumor therapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2003

Transcription factor c-Jun activation represses mdr-1 gene expression.

Expression of mdr-1 is complex and highly regulated. Several lines of evidence indirectly suggest that transcription factor c-Jun may negatively regulate human mdr-1 gene expression. We recently found that salvicine, a novel topoisomerase II inhibitor, is cytotoxic for multidrug resistance (MDR) tumor cells and down-regulates mdr-1 expression in MDR K562/A02 cells. Salvicine also stimulates a significant increase in the level of c-jun mRNA in HL60 cells. This study investigated the relationship between c-Jun activation and down-regulation of mdr-1 expression by salvicine in K562/A02 cells. Reverse-transcription PCR and Western blotting analyses revealed that salvicine suppressed mdr-1 expression in MDR cells and promoted c-jun expression in both MDR and parental K562 cells. Moreover, levels of c-jun expression were enhanced by salvicine before reduction of mdr-1 expression in K562/A02 cells. Furthermore, c-jun antisense oligodeoxynucleotides prevented salvicine-stimulated enhancement of c-Jun protein and reduction of mdr-1 gene expression, but did not affect the increase in c-jun mRNA levels. Salvicine promoted phosphorylation of c-Jun-N-terminal kinase and c-Jun protein in MDR K562/A02 and parental K562 cells. Electrophoretic mobility shift assay analysis showed that salvicine enhanced DNA binding activity of transcription factor activator protein 1. Additionally, c-jun antisense oligodeoxynucleotides also inhibited salvicine-induced apoptosis and cytotoxicity in MDR and parental K562 cells. A possible pathway emerges from these results: salvicine stimulates c-Jun-N-terminal kinase phosphorylation and activation, resulting in c-Jun phosphorylation and activation. Activated c-Jun promotes expression of c-jun itself, represses mdr-1 transcription, and triggers pro-apoptotic signals, resulting in low mdr-1 expression and cell death. The present results demonstrate that transcription factor c-Jun plays a principal role in down-regulation of mdr-1 expression and induction of apoptosis in salvicine-treated human MDR K562/A02 cells, providing new insights into the complicated mechanisms regulating mdr-1 expression. The findings also suggest that c-Jun might be a potential drug target for circumventing tumor MDR.

Apoptosis↗

PubMed2003

Monofunctional platinum complexes showing potent cytotoxicity against human liver carcinoma cell line BEL-7402.

Three novel Pt(II) complexes [PtL(1)'Cl] I (L(1)' = glycine-N'-8-quinolylamide), [PtL(2)'Cl] II (L(2)' = l-alanine-N'-8-quinolylamide), and [PtL(3)Cl] III [L(3) = N-(tert-butoxycarbonyl)-l-methionine-N'-8-quinolylamide] have been synthesized and characterized. The crystal structure of complexes II and III showed that the ligands are three-coordinated with only one Cl(-) as the leaving group. Complex II crystallized in the monoclinic system with space group P2(1), a = 9.502(2) A, b = 4.724(1) A, c = 14.800(3) A, while complex III crystallized in the orthorhombic system with space group P2(1)2(1)2(1), a = 5.441(1) A, b = 12.978(3) A, c = 29.438(6) A. These complexes have been tested against a wide range of tumor cell lines including BEL-7402, HCT-116, SPC-A4, MOLT-4, P388, HL-60, A-549, SGC-7901, MKN-28, and HO-8910. Complex III is highly cytotoxic against the HCT-116 (IC(50) = 0.38 microM), SPC-A4 (IC(50) = 0.43 microM), BEL-7402 (IC(50) = 0.43 microM), and MOLT-4 (IC(50) = 0.61 microM) cell lines. The cell line most sensitive to III is human liver carcinoma cell line BEL-7402, which has a response rate of 75.1% at 6.6 x 10(-7) M, nearly 6 times higher than that of cisplatin.

Antineoplastic Agents↗