• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.2
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• pp.194-201
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• 2016

The anti-inflammatory activity of ethanol extract from Chondrus nipponicus Yendo (CNYEE) was investigated by measuring production of a lipopolysaccharide-induced inflammatory response mediator. CNYEE had no cytotoxic effects on proliferation of macrophages compared to the control. CNYEE significantly inhibited (over 50%) NO production at $50{\mu}g/mL$, with inhibitory effects on expression levels of cytokines such as interleukin (IL)-6, tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and IL-$1{\beta}$. In particular, IL-6 inhibitory activity of CNYEE was higher than 70% at $100{\mu}g/mL$. CNYEE also reduced protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor (NF)-${\kappa}B$ in a dose-dependent manner. CNYEE also significantly reduced phosphorylation of p38, extracellular signal-regulated kinase, and c-Jun N-terminal kinase. Therefore, these results suggest that CNYEE may have anti-inflammatory effects by modulating the NF-${\kappa}B$ and mitogen-activated protein kinases signaling pathways and may be used as an anti-inflammatory therapeutic material.

• Microbiology and Biotechnology Letters
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• v.44 no.4
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• pp.442-451
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• 2016

The aim of this study was to investigate the anti-inflammatory effect of Sargassum miyabei Yendo ethanol extract (SMYEE) using RAW 264.7 cells and croton oil-induced Balb/c mice. SMYEE inhibited the production of pro-inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor $(TNF)-{\alpha}$, and $IL-1{\beta}$] and nitric oxide in lipopolysaccharide (LPS)-induced inflammatory response. In addition, SMYEE suppressed the expression of inducible nitric oxide, cyclooxygenase-2, and nuclear factor-kappa B. Further, SMYEE inhibited the expression of mitogen-activated protein kinases (MAPKs), such as extra cellular signal-regulated kinase 1/2, p38, and c-Jun N-terminal kinase. In ear edema test, edema formation in the SMYEE treatment was lower than that in the positive control and was similar to that in the prednisolone treatment group. Photomicrographs of mice ear tissue showed a reduction in dermal thickness and number of infiltrated mast cells. Therefore, our results indicate that SMYEE exerts an anti-inflammatory effect via inhibition of nuclear factor ${NF}-{\kappa}B$ and MAPK activation and can be used as a natural source of anti-inflammatory compounds.

• Journal of Ginseng Research
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• v.36 no.3
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• pp.242-247
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• 2012

Chondrocyte apoptosis has been recognized as an important factor in the pathogenesis of osteoarthritis (OA). Hydrogen peroxide ($H_2O_2$), which produces reactive oxygen species, reportedly induces apoptosis in chondrocytes. The ginsenoside $Rb_1$ (G-$Rb_1$) is the principal component in ginseng and has been shown to have a variety of biological activities, such as anti-arthritis, anti-inflammation, and anti-tumor activities. In this study, we evaluated the effects of G-$Rb_1$ on the mitochondrial permeability transition (MPT) and caspase-3 activity of chondrocyte apoptosis induced by $H_2O_2$. Cultured rat articular chondrocytes were exposed to $H_2O_2$ with or without G-$Rb_1$ and assessed for viability, MPT, Bcl-xL/Bax expression, caspase-3 activity, and apoptosis. The co-treatment with G-$Rb_1$ showed an inhibition of MPT, caspase-3 activity, and cell death. Additionally, the levels of the apoptotic protein Bax were significantly lower and the levels of the anti-apoptotic protein Bcl-xL were higher compared with $H_2O_2$ treatment alone. The results of this study demonstrate that G-$Rb_1$ protects chondrocytes against $H_2O_2$-induced apoptosis, at least in part via the inhibition of MPT and caspase-3 activity. These results demonstrate that G-$Rb_1$ is a potentially useful drug for the treatment of OA patients.

• Journal of Life Science
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• v.28 no.4
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• pp.488-495
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• 2018

The p53 gene plays a critical role in the transcriptional regulation of cellular response to stress, DNA damage, hypoxia, and tumor development. Keeping in mind the recently discovered manifold physiological functions of p53, its involvement in the regulation of cancer is not surprising. In about 50% of all human cancers, inactivation of p53's protein function occurs either through mutations in the gene itself or defects in the mechanisms that activate it. This disorder plays a crucial role in tumor evolution by allowing the evasion of a p53-dependent response. Many recent studies have focused on directly targeting p53 mutants by identifying selective, small molecular compounds to deplete them or to restore their tumor-suppressive function. These small molecules should effectively regulate various interactions while maintaining good drug-like properties. Among them, the discovery of the key p53-negative regulator, MDM2, has led to the design of new small molecule inhibitors that block the interaction between p53 and MDM2. Some of these small molecule compounds have now moved from proof-of-concept studies into clinical trials, with prospects for further, more personalized anti-carcinogenic medicines. Here, we review the structural and functional consequences of wild type and mutant p53 as well as the development of therapeutic agents that directly target this gene, and compounds that inhibit the interaction between it and MDM2.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.4
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• pp.856-859
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• 2007

We have investigated the antimetastatic and antitumor effects of Ginsenoside Rh2 and ${\beta}-glucan$ unsing an experimental metastatic mouse model intravenously injected with B 16 melanoma F 10 cells. Animal groups are divided into six groups according to the dosage of drug administration and the kind of drugs. The groups are control, ${\beta}-glucan$ with 50, 100 and 200 mg/kg, Geinsenoside Rh2 50 mg/kg, and ${\beta}-glucan$ 50 mg/kg + Ginsenoside Rh2 50 mg/kg. Oral administration of various concentration of ${\beta}-glucan$( 50, 100, and 200 mg/kg) were reduced the lung- metastatics induced by metastatic B16 melanoma F 10 cells injection with a dose dependent manner in the syngenic mice. At same dosage group, Ginsenoside Rh2 (50 mg/kg) has more antimetastatic effect than the ${\beta}-glucan$(50 mg/kg). The highest antimetastatic effects was observed in the ${\beta}-glucan$ 50 mg/kg + Ginsenoside Rh2 50 mg/kg group and has a similar tendency in the anti-tumor effects, including decrease of the average tumor weight and increase of the average survival rate. There are no differences of the average tumor weights were apparent in the ${\beta}-glucan$ groups, however there were little decrease of the average tumor weight in Ginsenoside 50 mg/kg group and ${\beta}-glucan$ 50 mg/kg + Ginsenoside Rh2 50 mg/kg group than that of the control group. The rate of average survival rate in the ${\beta}-glucan$ 50 mg/kg + Ginsenoside Rh2 50 mg/kg group, ${\beta}-glucan$ 200 mg/kg, ${\beta}-glucan$ 100 mg/kg and ${\beta}-glucan$ 50 mg/kg, and Ginsenoside 50 mg/kg groups were highly in order. These data suggest that antimetastatic and antitumor effect of combination of Ginsenodide Rh2 and ${\beta}-glucan$ be the highest in this study.

• The Journal of the Korean bone and joint tumor society
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• v.4 no.1
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• pp.13-21
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• 1998

Taxol, the extract from the Taxus brevifolia which is a Pacific yew tree has aroused the interest of the tumor investigators since the 1960s. As well, it is shown to have broad antitumor activity in preclinical experimental models. Its action mechanism is an anti-microtubule effect by duplication of tubulin. The most impressive antitumor activity of taxol has been observed in advanced ovarian cancer and metastatic breast cancer. The purpose of this study was to determine how taxol acts on malignant bone tumor cell lines, to compare its cytotoxic effect with those of other chemotherapeutic agents, and to ascertain the its combination effect with adriamycin. Cell lines used in this study were G-292(osteosarcoma, human), SaOS-2(osteosarcoma, primary, human), and HT-1080(fibrosarcoma, human). Methotrexate, adriamycin, cisplatinum, ifosfamide and taxol were used as testing chemotherapeutic agents and their maximum test concentration were $500{\mu}g/ml$, $200{\mu}g/ml$, $500{\mu}g/ml$, $1000{\mu}g/ml$, and $600{\mu}g/ml$, respectively. The media for cell culture was RPMI-1640 with 10% fetal bovine serum and gentamycin. The results were as follows. The $IC_{50}$ of methotrexate, ifosfamide, cisplatinum, adriamycin and Taxol in G-292 were $2.3{\times}10^{-1}{\mu}g/ml$, $8.0{\times}10^0{\mu}g/ml$, $3.5{\times}10^0{\mu}g/ml$, $9.8{\times}10^{-1}{\mu}g/ml$, $2.7{\times}10^{-2}{\mu}g/ml$ respectively, in SaOS-2 $3.5{\times}10^{-1}{\mu}g/ml$, $1.5{\times}10^1{\mu}g/ml$, $2.8{\times}10^0{\mu}g/ml$, $9.9{\times}10^{-2}{\mu}g/ml$, $1.0{\times}10^{-2}{\mu}g/ml$, respectively, in HT-1080 $4.2{\times}10^{-2}{\mu}g/ml$, $5.4{\times}10^1{\mu}g/ml$, $3.8{\times}10^0{\mu}g/ml$, $5.5{\times}10^{-3}{\mu}g/ml$, $1.1{\times}10^{-3}{\mu}g/ml$, respectively. In conclusion, taxol had very potent cytotoxic effect on the malignant bone tumor cell lines with adriamycin, and was more potent than methotrexate, cisplatinum and ifosfamide. There were synergistic antitumor effects on G-292 and SaOS-2 cell lines in combination test of taxol and adriamycin. From the above results, it would be estimated that taxol could be a new antitumor drug for the malignant bone tumors, providing measures against the side effects and followed by the clinical tests.

• Journal of Life Science
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• v.28 no.7
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• pp.778-785
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• 2018

Autophagy is a complex signaling process and has been implicated in tumor suppression and anticancer therapy resistance. Autophagy can produce tumor-suppressive effect by inducing autophagic cell death, either in collaboration with apoptosis. In this current study, we found that celecoxib (CCB), a nonsteroidal anti-inflammatory drug (NSAID) with multifaceted effects, induced autophagy including enhanced LC3 conversion (LC3-I to LC3-II) and reduced autophagy substrate protein p62 level in multidrug-resistant (MDR) cancer cells. CCB sensitized human multidrug resistant (MDR) cancer cells to the ansamycin-based HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG), a benzoquinoid ansamycin, which causes the degradation of several oncogenic and signaling proteins, by inducing autophagic cell death and apoptosis. CCB significantly augmented 17-AAG-mediated level of LC3-II/LC-I, indicating the combined effect of 17-AAG and CCB on the induction of autophagy. Autophagic degradation of mutant p53 (mutp53) and activation of caspase-3 in 17-AAG-treated MDR cells were accelerated by CCB. Inhibition of caspase-3-mediated apoptotic pathway by Z-DEVD-FMK, a caspase-3 inhibitor, did not completely block CCB-induced cell death in MCF7-MDR cells. In addition, treatment of MDR cells with Z-DEVD-FMK failed to prevent activation of autophagy by combined treatment with 17-AAG and CCB. Based on our findings, the ability of clinically used drug CCB to induce autophagy has important implications for its development as a sensitizing agent in combination with Hsp90 inhibitor of MDR cancer.

• Korean Journal of Clinical Laboratory Science
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• v.55 no.4
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• pp.306-313
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• 2023

Sepsis is a systemic inflammatory response, with manifestations in multiple organs by pathogenic infection. Currently, there are no promising therapeutic strategies. Signal transducer and activator of transcription 3 (STAT3) is a cell signaling transcription factor. Niclosamide is an anti-helminthic drug approved by the Food and Drug Administration (FDA) as a potential STAT3 inhibitor. C57BL/6 mice were treated with an intraperitoneal injection of lipopolysaccharide (LPS). Niclosamide was administered orally 2 hours after the LPS injection. This study found that Niclosamide improved the survival and lung injury of LPS-induced mice. Niclosamide decreased the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) in serum. The effects of Niclosamide on phosphoinositide 3-kinase (PI3K), AKT, nuclear factor-κB (NF-κB), and STAT3 signaling pathways were determined in the lung tissue by immunoblot analysis. Niclosamide reduced phosphorylation of PI3K, AKT, NF-κB, and STAT3 significantly. Furthermore, it reduced the phosphorylation of STAT3 by LPS stimulation in RAW 264.7 macrophages. Niclosamide also reduced the LPS-stimulated expression of proinflammatory mediators, including IL-6, TNF-α, and IL-1β. Niclosamide provides a new therapeutic strategy for murine sepsis models by suppressing the inflammatory response through STAT3 inhibition.

• Journal of Life Science
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• v.19 no.8
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• pp.1073-1080
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• 2009

A number of studies have demonstrated that the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce the risks of colorectal, oesophageal and lung cancers. NSAIDs have been shown to exert their anti-cancer effects through inducing apoptosis in cancer cells. The susceptibility of tumor cells to anti-tumor drug-induced apoptosis appears to depend on the balance between pro-apoptotic and anti-apoptotic programs such as nuclear factor kB (NF-kB), phosphatidylinositol 3-kinase (PI3K)-Akt/protein kinase B (PKB) and MEK1/2-ERK1/2 pathways. We examined the effects of pro-survival PI3K and ERK1/2 signal pathways on cell cycle arrest and apoptosis in response to NSAIDs including sulindac sulfide and NS398. We show that simultaneous inhibition of the Akt/PKB and ERK1/2 signal cascades could synergistically enhance the potential pro-apoptotic activities of sulindac sulfide and NS398. Similar enhancement was observed in cells treated with sulindac sulfide or NS398 and 100 ${\mu}$M genistein, an inhibitor of receptor tyrosine kinases (RTKs) that are upstream of PI3K and MEK1/2 signaling. We further demonstrate that NAG-1 is induced and plays a critical role(s) in apoptosis by NSAIDs-based combined treatment. In sum, our results show that combinatorialtreatment of sulindac sulfide or NS398 and genistein results in a highlysynergistic induction of apoptotic cell death to increase the chemopreventive effects of the NSAIDs, sulindac sulfide and NS398.

• Biomolecules & Therapeutics
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• v.17 no.4
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• pp.403-411
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• 2009

Thiacremonone, the main component isolated from heated garlic (Allium sativum L.), is interested for using as a cancer preventive or therapeutic agent since garlic has been known to be useful plant in the treatment of cancers. Nuclear factor kappaB (NF-${\kappa}B$) is constitutively activated in the prostate cancer and activation of NF-${\kappa}B$ is implicated in drug resistance in cancer cells. Docetaxel, a semisynthetic analog of paclitaxel, is an antineoplastic drug widely used for advanced various cancer. In previous studies, we found that thiacremonone inhibited activation of NF-${\kappa}B$ in cancer cells and marcrophages. In the present study, we investigated whether thiacremonone could increase susceptibility of prostate cancer cells (PC-3 and DU145) to docetaxel via inactivation of NF-${\kappa}B$. We found that the combination treatment of thiacremonone (50 ${\mu}g$/ml) with docetaxel (5 nM) was more effective in the inhibition of prostate cancer cell growth and induction of apoptosis accompanied with the significant inhibition of NF-${\kappa}B$ activity than those by the treatment of thiacremonone or docetaxel alone. It was also found that NF-${\kappa}B$ target gene expression of Bax, caspase-3 and caspase-9 was much more significantly enhanced, but the expression of Bcl-2 was also much more significantly inhibited by the combination treatment. These results indicate that thiacremonone inhibits NF-${\kappa}B$, and enhances the susceptibility of prostate cancer cells to docetaxel. Thus, thiacremonone could be useful as an adjuvant anti-cancer agent.