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Sun Y.-J.,Shenyang Pharmaceutical University | Li Z.-L.,Shenyang Pharmaceutical University | Chen H.,Tianjin Key Laboratory for Biomarkers of Occupational and Environmental Hazard | Liu X.-Q.,Shenyang Pharmaceutical University | And 2 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2011

Three new aryltetralin lignans, 4-acetyl-4-demethyl-podophyllotoxin (1) and sinolignans A, B (2-3), and two new natural products (4-5), were isolated from the roots and rhizomes of Sinopodophyllum emodi together with twelve known lignans (6-17). Their structures and stereochemistry were elucidated on the basis of spectroscopic evidence, and circular dichroism (CD) method. The cytotoxic activities of all isolated compounds were evaluated against HeLa and KB cell lines. Compared with etoposide, compounds 1, 6-9, and 13 showed more potent cytotoxicities against two tumor cell lines. On the basis of IC 50 values, deoxypodophyllotoxin (7) was about 579 and 1123 times more toxic than etoposide in HeLa and KB cell lines, respectively. The preliminary SAR study indicated that an oxygenated group at C-7′ might decrease cytotoxicity against two cell lines, which was different from most previous studies. However, this needs to be systematically verified by extensive pharmacological experiments. © 2011 Elsevier Ltd. All rights reserved. Source


Wang Y.,Tianjin Key Laboratory for Biomarkers of Occupational and Environmental Hazard
Zhonghua fu chan ke za zhi | Year: 2010

To study the mechanism of chemotherapy resistance caused by interleukin-6 (IL-6) in ovarian cancer cells and its related signal pathways. Ovarian cancer cell lines A2780 (IL-6 receptor positive, while non-IL-6-expressing and cisplatin/paclitaxel-responsive) and SKOV3 cell lines (overexpressing of IL-6 receptor and IL-6 and cisplatin/paclitaxel-resistant) were suitable models for this study. The effect of exogenous (a short period of treatment with recombination IL-6) and endogenous IL-6 (by transfecting with plasmid encoding for sense IL-6) in A2780 cells or deleting of endogenous IL-6 expression in SKOV3 cells (by transfecting with plasmid encoding for antisense IL-6) on the sensitivity to cisplatin and paclitaxel was investigated. Meanwhile, the mechanism of chemotherapy resistance caused by IL-6 in ovarian cancer cells and its related signal pathways were also analyzed. We found that both exogenous and endogenous IL-6 induce cisplatin and paclitaxel resistance in non-IL-6-expressing A2780 cells (the resistance multiple to cisplatin and paclitaxel was: exogenous, 6.25 and 7.31; endogenous, 7.13-8.34 and 7.61-10.70), while deleting of endogenous IL-6 expression in IL-6-overexpressing SKOV3 cells promotes its sensitivity to anticancer drugs (the resistance multiple to cisplatin and paclitaxel was 0.15 and 0.10, 0.10 and 0.08). IL-6 significantly up-regulated the expression levels of mRNA and protein of drug resistance-associated genes, MDR1 and GST-π, and apoptosis-inhibiting genes, bcl-2, bcl-xL and XIAP in a dose-dependent manner in A2780 cells. In accordance with this finding, the mRNA and protein levels of MDR1 and GST-π enhanced in sense IL-6-transfected A2780 cells, and reduced in antisense IL-6-transfected SKOV3 cells compared with the corresponding parental and control vector-transfected cells, which had no difference. It was found that PD98059 [mitogen-activated protein kinase-extracellular signal-regulated kinase (MEK) inhibitor] and wortmannin [phosphatidylinositol 3-kinase (PI3K) inhibitor] significantly antagonized IL-6-induced phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B (Akt), respectively, and both of them blocked IL-6-induced cisplatin and paclitaxel resistance and the inhibitory effects of PD98059 and wortmannin were dependent on its concentration. These data suggest that IL-6-induced chemoresistance may be associated with increase of both drug resistance-associated genes (MDR1 and GST-π) and apoptosis-inhibiting genes (bcl-2, bcl-xL and XIAP), and activation of MEK/ERK and PI3K/Akt. Therefore, modulation of IL-6 expression or its related signaling pathway may be a promising strategy of treatment for drug-resistant ovarian cancer. Source


Liu D.-L.,Tianjin Key Laboratory for Biomarkers of Occupational and Environmental Hazard | Qiu F.,Shenyang Pharmaceutical University
Journal of Asian Natural Products Research | Year: 2011

Microbial transformation of oleanolic acid (1) was carried out. Six transformed products (2-7) from 1 by Alternaria longipes and three transformed products (8-10) from 1 by Penicillium adametzi were isolated. Their structures were elucidated as 2,3,19-trihydroxy-ursolic acid-28-O - d-glucopyranoside (2), 2,3,19-trihydroxy-ursolic acid-28-O - d-glucopyranoside (3), oleanolic acid 28-O - d-glucopyranosyl ester (4), oleanolic acid-3-O - d-glucopyranoside (5), 3-O-(-d-glucopyranosyl)-oleanolic acid-28-O - d-glucopyranoside (6), 2,3,19a-trihydroxy-oleanolic acid-28-O - d-glucopyranoside (7), 21-hydroxyl oleanolic acid-28-O - d-glucopyranoside (8), 21-hydroxyl oleanolic acid (9), and 7,21-dihydroxyl oleanolic acid (10) based on the extensive NMR studies. Among them, 10 was a new compound and compounds 5 and 8-10 had stronger cytotoxic activities against Hela cell lines than the substrate. At the same time, it was reported for the first time in this paper that the skeletons of compounds 2 and 3 were changed from oleanane to uranane and seven glycosidation products were obtained by biotransformation. © 2011 Taylor & Francis. Source


Sun Y.-J.,Shenyang Pharmaceutical University | Li Z.-L.,Shenyang Pharmaceutical University | Chen H.,Tianjin Key Laboratory for Biomarkers of Occupational and Environmental Hazard | Liu X.-Q.,Shenyang Pharmaceutical University | And 2 more authors.
Planta Medica | Year: 2012

Four new tetrahydrofuranoid lignans, (-)-tanegool-7′-methyl ether (1), (+)-7′-methoxylariciresinol (2), sinolignan C (3), and epipinoresinol-4,4-di-Oβ- D-glucopyranoside (4), were isolated from the roots and rhizomes of Sinopodophyllum emodi together with one known lignan (5). Their structures and stereochemistry were elucidated on the basis of spectroscopic and mass spectrometric evidence. The isolation of compounds 1-5 represents the first report of tetrahydrofuran lignans from the genus Sinopodophyllum. The cytotoxic activities of all isolated compounds were evaluated against HeLa and KB cell lines, and compound 1 showed the most potent cytotoxicity with ICvalues of 9.7 μM and 4.7 μM, respectively. Source


Meng B.,Institute of Health and Environmental Medicine | Meng B.,Tianjin Key Laboratory for Biomarkers of Occupational and Environmental Hazard | Gao W.,Institute of Health and Environmental Medicine | Wei J.,Institute of Health and Environmental Medicine | And 4 more authors.
Nutrition | Year: 2013

Objective: The aim of this study was to determine the effects of quercetin on homocysteine (Hcy) metabolism and hepatic antioxidant status in high methionine (Met)-fed rats. Methods: Rats were fed for 6 wk the following diets: control, 1.0% Met, 1.0% Met and 0.1% quercetin, 1.0% Met and 0.5% quercetin, 1.0% Met and 2.5% quercetin-supplemented diets. Serum Hcy, Met, cysteine, serine, taurine, glutathione (GSH), quercetin and its metabolites, and activities of alanine transaminase (ALT) and aspartate transaminase (AST) were assayed. Hepatic malondialdehyde, GSH and carbonyls, and activity of superoxide dismutase and ferric-reducing antioxidant power also were measured. Results: Serum Hcy was increased significantly after Met treatment and decreased after quercetin supplementation. Meanwhile, serum taurine was increased and serine decreased. However, the content of GSH in serum and liver was decreased in the quercetin-supplemented groups and activities of serum ALT and AST were enhanced in the 1.0% Met and 2.5% quercetin-supplemented groups. Conclusions: Quercetin is effective in decreasing serum Hcy level in high Met-fed rats and one of possible mechanisms is associated with increased transsulfuration of Hcy. Quercetin can acts as a prooxidant at high intake levels. © 2013 Elsevier Inc. Source

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