Publications (122) View all
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Article: The phenyl-thiophenyl propenone RK-I-123 reduces the levels of reactive oxygen species and suppresses the activation of NF-κB and AP-1 and IL-8 expression in Helicobacter pylori-infected gastric epithelial AGS cells.
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ABSTRACT: OBJECTIVE: To investigate whether the phenyl-thiophenyl propenone RK-I-123 suppresses interleukin-8 (IL-8) expression and activation of mitogen-activated protein kinases (MAPKs) and transcription factors (nuclear factor-κB [NF-κB] and activator protein-1 [AP-1]) by reducing reactive oxygen species (ROS) levels in Helicobacter pylori-infected gastric epithelial cells. MATERIAL: Helicobacter pylori in Korean isolates, human gastric epithelial AGS cells. TREATMENT: AGS cells pretreated with or without RK-I-123 were cultured in the presence of H. pylori at a bacterium/cell ratio of 300:1. METHODS: Reactive oxygen species and IL-8 levels were determined by dichlorofluorescein fluorescence and enzyme-linked immunosorbent assay. The IL-8 mRNA expression was analyzed by the real-time reverse transcription-polymerase chain reaction (RT-PCR). The MAPK and IκBα levels were determined by western blotting. The activation of NF-κB and AP-1 was determined by the electrophoretic mobility shift assay. RESULTS: Helicobacter pylori induced an increase in ROS and IL-8 expression and activation of MAPKs and transcription factors (NF-κB and AP-1) together with the degradation of IκBα in AGS cells, all of which were inhibited by RK-I-123. CONCLUSIONS: The RK-I-123 suppressed the H. pylori-induced IL-8 expression and activation of MAPKs, NF-κB, and AP-1 by reducing ROS levels in AGS cells. The RK-I-123 may be a potential candidate for the treatment of H. pylori-induced gastric inflammation.Agents and Actions 04/2013; · 1.59 Impact Factor -
Article: Globular Adiponectin Modulates Expression of Programmed Cell Death 4 and miR-21 in RAW 264.7 macrophages through the MAPK/NF-κB pathway.
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ABSTRACT: MicroRNA-21 and programmed cell death 4 (PDCD4), a downstream target of miR-21, mediate diverse physiological responses. Here we demonstrate that globular adiponectin (gAcrp) modulates expression of miR-21 and PDCD4 in RAW 264.7 macrophages. These effects were abrogated by inhibitors of ERK1/2, JNK or NF-κB. Conditioned media collected from gAcrp-stimulated RAW 264.7 macrophages caused similar effects as direct gAcrp treatment, showing the paracrine effect of gAcrp. These data indicate that gAcrp modulates the miR-21/PDCD4 axis through the ERK and JNK/NF-κB pathways in RAW 264.7 macrophages and further suggest that the miR-21/PDCD4 axis may be a novel target mediating adiponectin-induced biological responses.FEBS letters 04/2013; · 3.54 Impact Factor -
Article: Chalcones, inhibitors for topoisomerase I and cathepsin B and L, as potential anti-cancer agents.
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ABSTRACT: In order to diversify the pharmacological activity of chalcones and extend the scaffold of topoisomerase and cathepsins B and L inhibitors, we have designed and synthesized total 18 chalcone compounds and tested their biological activity. In the topoisomerase inhibition test, most analogues in group III and IV except compound 11 exhibited more efficient topoisomerase I inhibitory activity than camptothecin at 20μM. Compounds 15, 16 and 18 in group IV showed significant cathepsin B and L inhibitory activity. Among the compounds, compound 15 was most active with IC50 values of 1.81±0.05μM on cathepsin B and 3.15±0.07μM on cathepsin L, respectively. Compound 15 also showed most potent cytotoxic activity against T47D and SNU638 cells with IC50 values of 1.37±0.05μM and 0.62±0.01μM, respectively. Overall, although more compounds should be tested and analyzed for clear SAR against topoisomerase I and cathepsin B and L, compound 15 showed consistent inhibitory ability on the tested assays, which can implicate the cytotoxic activity of compound 15 on topoisomerase I and cathepsin B and L inhibitory pathways.Bioorganic & medicinal chemistry letters 04/2013; · 2.65 Impact Factor -
Article: Globular adiponectin inhibits ethanol-induced apoptosis in HepG2 cells through heme oxygenase-1 induction.
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ABSTRACT: Hepatocellular apoptosis is an essential pathological feature of alcoholic liver disease. Adiponectin, an adipokine predominantly secreted from adipose tissue, has been shown to play beneficial roles in alcoholic liver disease against various inflammatory and pro-apoptotic molecules. However, the effects of adiponectin on ethanol-induced apoptosis in liver cells are largely unknown. Herein, we investigated the role of globular adiponectin (gAcrp) in the prevention of ethanol-induced apoptosis and further tried to decipher the potential mechanisms involved. In the present study, we demonstrated that gAcrp significantly inhibits both ethanol-induced increase in Fas ligand expression and activation of caspase-3 in human hepatoma cell lines (HepG2 cells), suggesting that gAcrp plays a protective role against ethanol-induced apoptosis in liver cells. This protective effect of gAcrp was mediated through adiponectin receptor R1 (adipoR1). Further, globular adiponectin treatment caused induction of heme oxygenase-1 (HO-1) through, at least in part, nuclear factor (erythroid-derived 2)-like 2, (Nrf2) signaling. Treatment with SnPP, a pharmacological inhibitor of HO-1, and knockdown of HO-1 with small interfering RNA (siRNA) restored caspase-3 activity suppressed by gAcrp, indicating a critical role of HO-1 in mediating the protective role of gAcrp in ethanol-induced apoptosis in liver cells. In addition, carbon monoxide, a byproduct obtained from the catabolism of free heme was found to contribute to the anti-apoptotic effect of adiponectin. In conclusion, these data demonstrated that globular adiponectin prevents ethanol-induced apoptosis in HepG2 cells via HO-1 induction and revealed a novel biological response of globular adiponectin in the protection of liver injury from alcohol consumption.Biochemical pharmacology 07/2012; 84(7):974-83. · 4.25 Impact Factor -
Article: New topoisomerases inhibitors: synthesis of rutaecarpine derivatives and their inhibitory activity against topoisomerases.
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ABSTRACT: A series of rutaecarpine derivatives were prepared by employing previously reported methods and their inhibitory activities against topoisomerase I and II were evaluated. Among them, strongly cytotoxic 10-bromorutaecarpine and 3-chlororutaecarpine showed strong inhibitory activities against topo I and II.Archives of Pharmacal Research 05/2012; 35(5):785-9. · 1.59 Impact Factor
