• Journal of Sasang Constitutional Medicine
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• v.21 no.1
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• pp.139-149
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• 2009

1. Objectives The roots of Sophora flavescens Aiton (SFA) are widely used as a herbal remedy for allergic inflammation. In this study, we invested the effect of SFA on passive cutaneous anaphylaxis reaction and histamin releas and we demonstrated that SFA suppressed the production of pro-inflammatory cytokines, such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin- 6 (IL-6), and interleukin -8 (IL-8), through inhibition of the $NF{\kappa}B$, JNK and p38 pathway in the human mast cell line, HMC-1. 2. Methods To accomplish this, we invested passive cutaneous anaphylaxis reaction and histamin release at an animal experiment. In addition, we investigated the effect of SFA on the production of inflammation-related cytokines in HMC-1 cells that were co-treated with PMA and A23187, which can induce production of pro-inflammatory cytokines. 3. Results and Conclusions SFA induced passive cutaneous anaphylaxis reaction and histamin releas and supressed the expression of TNF-${\alpha}$, IL-6, and IL-8. In addition, the protein levels of TNF-${\alpha}$ were also decreased by SFA treatment. Furthermore, SFA inhibited the nuclear translocation of nuclear factor $NF{\kappa}B$ through inhibition of the phosphorylation and degradation of $I{\kappa}B-{\alpha}$, which is an inhibitor of $NF{\kappa}B$. Moreover, SFA also inhibited induction of MAPKs (JNK, p38) and $NF{\kappa}B$ promoter-mediated luciferase activity. Taken together, these results suggest that SFA could be used as a treatment for mast cell-derived allergic inflammatory diseases.

• Biomolecules & Therapeutics
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• v.27 no.1
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• pp.117-125
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• 2019

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has recently been noted as a repositioning candidate for angiogenesis inhibition and cancer therapy. However, the definite anti-angiogenic mechanism of MBZ remains unclear. In this study, we explored the inhibitory mechanism of MBZ in endothelial cells (ECs) and developed a novel strategy to improve its anti-angiogenic therapy. Treatment of ECs with MBZ led to inhibition of EC proliferation in a dose-dependent manner in several culture conditions in the presence of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) or FBS, without selectivity of growth factors, although MBZ is known to inhibit VEGF receptor 2 kinase. Furthermore, MBZ inhibited EC migration and tube formation induced by either VEGF or bFGF. However, unexpectedly, treatment of MBZ did not affect FAK and ERK1/2 phosphorylation induced by these factors. Treatment with MBZ induced shrinking of ECs and caused G2-M arrest and apoptosis with an increased Sub-G1 fraction. In addition, increased levels of nuclear fragmentation, p53 expression, and active form of caspase 3 were observed. The marked induction of autophagy by MBZ was also noted. Interestingly, inhibition of autophagy through knocking down of Beclin1 or ATG5/7, or treatment with autophagy inhibitors such as 3-methyladenine and chloroquine resulted in marked enhancement of anti-proliferative and pro-apoptotic effects of MBZ in ECs. Consequently, we suggest that MBZ induces autophagy in ECs and that protective autophagy can be a novel target for enhancing the anti-angiogenic efficacy of MBZ in cancer treatment.

• Journal of Embryo Transfer
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• v.33 no.4
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• pp.287-296
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• 2018

Ganglioside GM3 is known as an inhibition factor of cell differentiation and proliferation via inhibition of epidermal growth factor receptor (EGFR) phosphorylation. Our previous study showed that the exogenous ganglioside GM3 reduced the meiotic maturation of porcine oocytes and induced apoptosis at 44 h of in vitro maturation (IVM). However, the role of ganglioside GM3 in the relationship between EGFR signaling and apoptosis during porcine oocyte maturation has not yet been studied. First, porcine cumulus-oocyte complexes (COCs) were cultured in the NCSU-23 medium with exogenous ganglioside GM3 according to maturation periods (non-treated, only IVM I: 0 - 22 h, only IVM II: 22 - 44 h and IVM I & II: 0 - 44 h). We confirmed that the proportion of germinal vesicle breakdown (GVBD) increased significantly in the IVM I treated group than in the control group. We also confirmed that the meiotic maturation until M II stage and polar body formation decreased significantly in the only IVM I treated group. Cumulus cell expansion and mRNA levels of the expansion-related factors (HAS2, TNFAIP6 and PTX3) decreased significantly in the IVM I treated group than in the control group. Protein levels of EGFR, p-EGFR, ERK1/2, and p-ERK1/2 decreased significantly in the GM3-treated groups, during the IVM I period. In addition, cellular apoptosis, determined using TUNEL assay, and protein levels of Cleaved caspase 3, were increased significantly in the GM3-treated COCs during the IVM I period. Based on these results, ganglioside GM3 exposure of porcine COCs during the IVM I period reduced meiotic maturation and cumulus cell expansion via inhibition of EGFR activity in pigs.

• Journal of Microbiology and Biotechnology
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• v.32 no.4
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• pp.493-503
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• 2022

Forkhead transcription factor 3a (Foxo3a) is believed to be a tumor suppressor as its inactivation leads to cell transformation and tumor development. However, further investigation is required regarding the involvement of the activating transcription factor 3 (ATF3)-mediated Tat-interactive protein 60 (Tip60)/Foxo3a pathway in cancer cell apoptosis. This study demonstrated that Chelidonium majus upregulated the expression of ATF3 and Tip60 and promoted Foxo3a nuclear translocation, ultimately increasing the level of Bcl-2-associated X protein (Bax) protein. ATF3 overexpression stimulated Tip60 expression, while ATF3 inhibition by siRNA repressed Tip60 expression. Furthermore, siRNA-mediated Tip60 inhibition significantly promoted Foxo3a phosphorylation, leading to blockade of Foxo3a translocation into the nucleus. Thus, we were able to deduce that ATF3 mediates the regulation of Foxo3a by Tip60. Moreover, siRNA-mediated Foxo3a inhibition suppressed the expression of Bax and subsequent apoptosis. Taken together, our data demonstrate that Chelidonium majus induces SKOV-3 cell death by increasing ATF3 levels and its downstream proteins Tip60 and Foxo3a. This suggests a potential therapeutic role of Chelidonium majus against ovarian cancer.

• Journal of Applied Biological Chemistry
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• v.53 no.3
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• pp.139-146
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• 2010

The inhibitory effects of 25 polyphenols against in vitro allergic reactions were compared using biochemical and cell assays. Three polyphenols including curcumin, gallic acid, and quercetin suppressed the release of $\beta$-hexosaminidase from ionophore A23187-stimulated RBL-2H3 cells more effectively (>50% inhibition at $100{\mu}M$ concentration). They were found to have potencies in suppressing the release of histamine not only from ionophore A23187-, but also from immunoglobulin E (IgE)-stimulated RBL-2H3 cells. Moreover, such suppressive effects of the three polyphenols were also observed in A23187 plus PMA-costimulated rat peritoneal mast cells. The extent of inhibition were quantified as the respective polyphenol concentration that inhibit 50% ($IC_{50}$) of $\beta$-hexosaminidase or histamine release, showing an inhibition tendency with decreasing order of curcumin>gallic acid>quercetin. Down-regulation of $Ca^{2+}$ influx was suggested as the cause of the inhibition of $\beta$-hexosaminidase and histamine releases in these cells. The immune process inhibition was confirmed by the observed reduction in the gene expressions and release of pro-inflammatory cytokine tumor necrosis factor (TNF)-$\alpha$, interleukin (IL)-$1\beta$, and IL-4, due probably to antioxidant activity of the polyphenols. These findings illustrate that curcumin, gallic acid, and quercetin may be beneficial against allergic inflammatory diseases.

• Parasites, Hosts and Diseases
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• v.31 no.4
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• pp.379-381
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• 1993

We experienced the partial Inhibition of entry of Taxoplasma gondii Into MDCK cells when the FBS was depleted from media. MDCK cells and Toxoplasma (RH strains) were co-cultured, the penetration was inhibited up to 60-80% with concentration-dependence of FBS. Inhibitory effect was clear when the conc. of FBS was over 1% (v/v) with 50% inhibition comic. of 5%. When ToxopLosma was pre-incubated with FBS and then applied to MDCK cells, there were no inhibitory effect, but when FBS was added to Toxoplasma- MDCK co-culture, the time of adding was c10cal with rapid inhibition. And when FBS was further treated with heat ($95^{\circ}C$, 10 min), the Inhibitory effect was decreased slightiy in both raw and inactivated FBS. The FBS factor(s) might participate to neutralize secreted materials which enhancing penetration or Intervene between receptor-ligand blnding at the moment of entry through sterically rather than functionally.

• Applied Biological Chemistry
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• v.49 no.4
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• pp.298-303
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• 2006

The biological and antioxidative activity of Phellinus linteus extracts from gradient ethanol concentrations were examined. The phenol contents of Phellinus linteus(28.36 mg/100 ml) was higher in the 80% ethanol extracts than other extracts. Electron donation ability on DPPH of 80% and 90% ethanol extracts(94.12% and 94.14% inhibition) from Phellinus linteus were the highest. The antioxidant activity against water soluble materials of Phellinus linteus ethanol extracts showed totally high inhibition rates above 80%, especially in 80% and 90% ethanol extracts, they showed each 94.12% inhibition and 94.14% inhibition. The inhibition against ABTS [2,2azinobis(3-ethylbenzothiazoline-6-sulfonic acid)] radical decolorization of 80% ethanol extracts was the highest as 96.2%. The antioxidant protection factor (PF) against lipid soluble materials was the highest in 80% ethanol extracts as 1.69 PF, and TBARS of 80% and 90% ethanol extracts were lower as $1.15{\times}100{\mu}M$ and $1.21{\times}100{\mu}M$ than control($1.95{\times}100{\mu}M$. Angiotensin converting enzyme and xanthine oxidase inhibitory activity of 80% ethanol extracts from Phellinus linteus was higher as 95.10%, 85.07% than other extracts. The results to analized of simple phenolic compounds of Phellinus linteus ethanol extrcts with HPLC showed that they were procatecuic acid, caffeic acid and coumaric acid.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1457-1461
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• 2012

Purpose: Non small cell lung cancer (NSCLC) is the leading worldwide source of cancer-related deaths. Although some drugs targeting EGFR mutations have been developed, most advanced cases are still incurable. New targets for anticancer drugs are demanded. The kringle 1 domain of hepatocellular growth factor alpha chain (HGFK1) is a potent anti-angiogenesis factor. It has also emerged as a potential anticancer factor in hepatocellular carcinoma (HCC). The expression of HGFK1 protein in patients with NSCLC has not been reported to date. Method: Here, we assessed HGFK1 expression by Western blotting in 103 cases with advanced NSCLC to investigate the impact of HGFK1 on survival. Results: Results revealed 33 (30.1%) patients were classified as high expressors, this being significantly associated with less remote metastasis (P = 0.002) but not with lymph node metastasis (P = 0.062). There was also a significant association between HGFK1 expression and tumor size (P = 0.025) as well as clinical stage (P = 0.012). Kaplan-Meier survival analysis showed that both overall survival (OS) and progression free survival (PFS) of patients with HGFK1 expression were longer than those of patients without HGFK1 expression (P = 0.004 and P = 0.001 respectively). HGFK1 reversed gefitinib inhibition in the resistent NSCLC cell line A431/GR but did not inhibit the proliferation of NSCLC cells A431 and A431/GR directly. Reversion of gefitinib inhibition in A431/GR cells by HGFK1 was related to decreased phosphorylation of ERK and STAT5. Conclusions: HGFK1 may be a useful prognostic factor of advanced NSCLC patients and a potential drug for gefitinib resistant patients.

• Korean Journal of Cognitive Science
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• v.17 no.3
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• pp.207-229
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• 2006

Two experiments examined the relation of working memory capacity and the inhibition mechanism in working memory. Experiment 1 demonstrated that the high WM span group inhibited irrelevant information selectively and the low WM span group maintained both relevant and irrelevant information within WM. Experiment 2 showed that there were similar patterns of response time between high and low WM span groups in the lexical decision task. These results suggest that the ability to maintain relevant information and inhibit irrelevant information selectively in WM is an important factor of individual differences in working memory.

• BMB Reports
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• v.50 no.11
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• pp.539-545
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• 2017

The Integrated Stress Response (ISR) refers to a signaling pathway initiated by stress-activated $eIF2{\alpha}$ kinases. Once activated, the pathway causes attenuation of global mRNA translation while also paradoxically inducing stress response gene expression. A detailed analysis of this pathway has helped us better understand how stressed cells coordinate gene expression at translational and transcriptional levels. The translational attenuation associated with this pathway has been largely attributed to the phosphorylation of the translational initiation factor $eIF2{\alpha}$. However, independent studies are now pointing to a second translational regulation step involving a downstream ISR target, 4E-BP, in the inhibition of eIF4E and specifically cap-dependent translation. The activation of 4E-BP is consistent with previous reports implicating the roles of 4E-BP resistant, Internal Ribosome Entry Site (IRES) dependent translation in ISR active cells. In this review, we provide an overview of the translation inhibition mechanisms engaged by the ISR and how they impact the translation of stress response genes.