• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.1 no.1
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• pp.167-190
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• 1995

Bikiwhan is one of the oriental medicines that have been used for the treatment of tumors since ancient times. However, the mechanism of the drug action is not closely surved. This study was made to investigate the effects of Bikiwhan on the innate immunity were analysed by measuring the functions of phagocytes, and those of specific immunity were analysed by measuring T and B cells activities. The followings are the results obtained from this study : 1. Bikiwhan has direct cytotoxic effects against human lymphoma cell lines (K562) in a dose dependent manner. 2. An administration of Bikiwhan increased allogenic immune response in the mouse. 3. An administration of Bikiwhan increased the antibodies formation against SRBC. 4. An administration of Bikiwhan enhanced the apperance of rosette forming cells in the spleen. 5. An administration of Bikiwhan decreased the delayed-type hypersensitivity against dinitrofluorobenzene. 6. An administration of Bikiwhan has no effect on natural killer cells. 7. Bikiwhan increased the phagocyte activity of peritoneal macrophages in vitro and in in vivo as well. 8. Bikiwhan depressed the formation of reactive oxygen intermediated in vitro and in vivo as well. 9. Bikiwhan has the capacity to make peritoneal macrophages secrete nitric oxide. The above results demonstrate that Bikiwhan has enhancing effects of immune responses against tumors by decreasing tissue demages caused by immune responses.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2002.10a
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• pp.170-170
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• 2002

College of Pharmacy, Ewha womans University, Seoul, 120-750, Korea 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent halogenated aromatic hydrocarbon congener that induces expression of several genes including CYP1A1. Exposure to TCDD results in many toxic actions such as carcinogenesis, hepatotoxicity, immune suppression, and reproductive and developmental toxicity. Dramatic differences in dioxin toxicity have been observed between the sexes of some animal species, suggesting hormonal modulation of dioxin action. Many studies have been reported and propose several mechanisms of anti-estrogenic effects of TCDD. In contrast, the effect of estrogen on the regulation of CYP1A1 are not clear at present. There are several reports showing conflicting results. It seems that induction/inhibition of CYP1A1 may be dependent on cell-type and concentration. The purpose of this study was to investigate the regulation of TCDD-induced CYP1A1 gene expression by estradiol and its metabolites. We examined whether estradiol and its metabolites altered TCDD-mediated induction of CYP1A1 enzyme activity. 17 ${\beta}$ estradiol and 16 ${\alpha}$ estriol at non cytotoxic concentrations caused a significant concentration dependent decline of TCDD-induced EROD activity To determine whether reduced EROD activity reflected altered CYP1A1 mRNA expression, we measured CYP1A1 mRNA level by RT-PCR. And to examine whether estradiol and its metabolites have effects on TCDD-induced CYP1A1 gene expression at the transcription level, we also peformed transient transfection with an AhR responsive reporter plasmid containing the 5' flanking region of the human CYP1A1 gene to examine whether estradiol and its metabolites have effects on TCDD-induced CYP1A1 gene expression at the transcription level.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.2
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• pp.149-153
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• 2014

Nausea and emesis are a major side effect and obstacle for chemotherapy in cancer patients. Employ of antiemetic drugs help to suppress chemotherapy-induced emesis in some patients but not all patients. Ginger, an herbal medicine, has been traditionally used to treat various kinds of diseases including gastrointestinal symptoms. Ginger is effective in alleviating nausea and emesis, particularly, for cytotoxic chemotherapy drug-induced emesis. Ginger-mediated antiemetic effect has been attributed to its pungent constituents-mediated inhibition of serotonin (5-HT) receptor activity but its cellular mechanism of action is still unclear. Emetogenic chemotherapy drugs increase 5-HT concentration and activate visceral vagal afferent nerve activity. Thus, 5-HT mediated vagal afferent activation is essential to provoke emesis during chemotherapy. In this experiment, water extract of ginger and its three major pungent constituent's effect on 5-HT-evoked responses were tested on acutely dispersed visceral afferent neurons with patch-clamp methods. The ginger extract has similar effects to antiemetic drug ondansetron by blocking 5-HT-evoked responses. Pungent constituents of the ginger, [6]-shogaol, [6]-gingerol, and zingerone inhibited 5-HT responses in a dose dependent manner. The order of inhibitory potency for these compounds were [6]-shogaol>[6]-gingerol>zingerone. Unlike well-known competitive 5-HT3 receptor antagonist ondansetron, all tested ginger constituents acted as non-competitive antagonist. Our results imply that ginger and its pungent constituents exert antiemetic effects by blocking 5-HT-induced emetic signal transmission in vagal afferent neurons.

• Korean Journal of Clinical Laboratory Science
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• v.39 no.2
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• pp.68-75
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• 2007

After reports on regression of cancer in humans and animals infected with microbial pathogens date back more than 100 years, much effort has been spent over the years in developing a wild type or attenuated bacterial and purified bacterial proteins for the treatment of cancer. Pseudomonas aeruginosa exotoxin A (ETA) is known to inhibit cell growth and trigger significant cell death in various cancer cells. Although ETA induces apoptosis of cancer cells, its exact mechanism of action is not known yet. Four different assays were performed in this study: morphological assessment of apoptotic cells, cell cytotoxity, annexin-V binding assay, and cell cycle analysis. The proliferation and survival of the K-562 cells treated with ETA were decreased in a dose dependent manner. In addition, the apoptotic body of K-562 cells was induced by ETA treatment in a dose dependent manner. The ETA-induced apoptosis was confirmed by annexin-V binding assay. Flow cytometric analysis was examined to ascertain whether ETA could arrest the cell cycle at the sub-G1 phase. Our results suggest that P. aeruginosa ETA inhibits cell growth and induces apoptosis in human leukemia K-562 cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.3
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• pp.779-784
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• 2005

Mast cells are a potent source of mediators that regulate the inflammatory response in allergic reaction. To evaluate the atopic allergic effect of Asiasari radix(AR), the author investigated a possible effect of AR on mast cell-mediated allergic reaction, cytokines secretion and mRNA expression in vivo and in vitro. In mice orally administered by AR (0.01, 0.1 and 1.0 g/kg) for 1 h, compound 48/80-induced ear swelling was significantly reduced (P < 0.05). AR had inhibitory effects on tumor necrosis factor $(TNF)-{\alpha}$, interleukin (IL)-8, and IL-6 secretion from HMC-1. Significant reduced levels of $TNF-{\alpha}$ mRNA was observed in the human mast cell line (HMC-1) with AR (1.0 mg/ml). In addition, AR had no cytotoxic effect on cell viability. These results suggest that AR contributes to the treatment of atopic allergic reactions, and that its action may be due to inhibition of cytokine secretion and mRNA expression in HMC-1.

• Toxicological Research
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• v.31 no.2
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• pp.97-104
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• 2015

The skin exposure to solar irradiation and photoreactive xenobiotics may produce abnormal skin reaction, phototoxicity. Phototoxicity is an acute light-induced response, which occurs when photoreacive chemicals are activated by solar lights and transformed into products cytotoxic against the skin cells. Multifarious symptoms of phototoxicity are identified, skin irritation, erythema, pruritis, and edema that are similar to those of the exaggerated sunburn. Diverse organic chemicals, especially drugs, are known to induce phototoxicity, which is probably from the common possession of UV-absorbing benzene or heterocyclic rings in their molecular structures. Both UVB (290~320 nm) and UVA (320~400 nm) are responsible for the manifestation of phototoxicity. Absorption of photons and absorbed energy (hv) by photoactive chemicals results in molecular changes or generates reactive oxygen species and depending on the way how endogenous molecules are affected by phototoxicants, mechanisms of phototoxcity is categorized into two modes of action: Direct when unstable species from excited state directly react with the endogenous molecules, and indirect when endogeneous molecules react with secondary photoproducts. In order to identify phototoxic potential of a chemical, various test methods have been introduced. Focus is given to animal alternative test methods, i.e., in vitro, and in chemico assays as well as in vivo. 3T3 neutral red uptake assay, erythrocyte photohemolysis test, and phototoxicity test using human 3-dimensional (3D) epidermis model are examples of in vitro assays. In chemico methods evaluate the generation of reactive oxygen species or DNA strand break activity employing plasmid for chemicals, or drugs with phototoxic potential.

• Biomolecules & Therapeutics
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• v.23 no.5
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• pp.407-413
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• 2015

Paraquat dichloride (N,N-dimethyl-4-4'-bipiridinium, PQ) is an extremely toxic chemical that is widely used in herbicides. PQ generates reactive oxygen species (ROS) and causes multiple organ failure. In particular, PQ has been reported to be an immunotoxic agrochemical compound. PQ was shown to decrease the number of macrophages in rats and suppress monocyte phagocytic activity in mice. However, the effect of PQ on macrophage cell viability remains unclear. In this study, we evaluated the cytotoxic effect of PQ on the mouse macrophage cell line, RAW264.7 and its possible mechanism of action. RAW264.7 cells were treated with PQ (0, 75, and $150{\mu}M$), and cellular apoptosis, mitochondrial membrane potential (MMP), and intracellular ROS levels were determined. Morphological changes to the cell nucleus and cellular apoptosis were also evaluated by DAPI and Annexin V staining, respectively. In this study, PQ induced apoptotic cell death by dose-dependently decreasing MMP. Additionally, PQ increased the cleaved form of caspase-3, an apoptotic marker. In conclusion, PQ induces apoptosis in RAW264.7 cells through a ROS-mediated mitochondrial pathway. Thus, our study improves our knowledge of PQ-induced toxicity, and may give us a greater understanding of how PQ affects the immune system.

• Journal of Marine Bioscience and Biotechnology
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• v.1 no.4
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• pp.243-251
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• 2006

Dideoxypetrosynol A, a polyacetylene from the marine sponge Petrosia sp., is known to exhibit significant selective cytotoxic activity against a small panel of human tumor cell lines, however, the mechanisms of which are poorly understood. In the present study, it was investigated the further possible mechanisms by which dideoxytetrosynol A exerts its anti-proliferative action in cultured human leukemia cell line U937. We observed that the proliferation-inhibitory effect of dideoxypetrosynol A was due to the induction of G1 arrest of the cell cycle and apoptosis, which effects were associated with up-regulation of cyclin D1 and down-regulation of cyclin E without any change in cyclin-dependent-kinases (Cdks) expression. Dideoxypetrosynol A markedly induced the levels of Cdk inhibitor p16/INK4a expression. Furthermore, down-regulation of phosphorylation of retinoblastoma protein (pRB) by this compound was associated with enhanced binding of pRB and the transcription factor E2F-1. The increase in apoptosis was associated with a dose-dependent up-regulation in pro-apoptotic Bax expression and activation of caspase-3 and caspase-9. Dideoxytetrosynol A decreased the levels of cyclooxygenase (COX)-2 mRNA and protein expression without significant changes in the levels of COX-1, which was correlated with a decrease in prostaglandin E2 (PGE2) synthesis. Furthermore, dideoxytetrosynol A treatment markedly inhibited the activity of telomerase, and the expression of human telomerase reverse transcriptase (hTERT), a main determinant of the telomerase enzymatic activity, was progressively down-regulated by dideoxytetrosynol A treatment in a dose-dependent fashion. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of dideoxytetrosynol A.

• Korean journal of applied entomology
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• v.41 no.4
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• pp.279-284
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• 2002

Flacherie symptom was found in the fifth instar larvae of silkworm, Bombyx mori. The bacterial pathogen was isolated from the hemolymph of the infected silkworm and identified. The isolated bacteria caused a significant flacherie pathogenicity to the fifth instar larvae of B. mori when $5{\times}10^{6}$ cfu (colony-forming unit) of the bacteria was injected into each larva. The infected larvae began to die at 6 days after injection and resulted in complete mortality at 10 days. The bacterium was identified as Staphylococcus gallinarum based on the morphological and physiological characteristics described in Bergey's manual. This identification was further supported by the characters of carbohydrate utility analyzed from a bacterial identification system ($MicroLog^{\circledR}$) and also by the molecular structure of 165-23S rDNA internal transcribed spaces. As an insecticidal action, S. gallinarum caused hemolymph septicemia by its cytotoxic effect on the hemocytes of B. mori.

• Journal of Microbiology and Biotechnology
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• v.27 no.2
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• pp.262-270
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• 2017

Yersinia enterocolitica is a well-known foodborne pathogen causing gastrointestinal infections worldwide. The strain Y. enterocolitica FORC_002 was isolated from the gill of flatfish (plaice) and its genome was sequenced. The genomic DNA consists of 4,837,317 bp with a GC content of 47.1%, and is predicted to contain 4,221 open reading frames, 81 tRNA genes, and 26 rRNA genes. Interestingly, genomic analysis revealed pathogenesis and host immune evasion-associated genes encoding guanylate cyclase (Yst), invasin (Ail and Inv), outer membrane protein (Yops), autotransporter adhesin A (YadA), RTX-like toxins, and a type III secretion system. In particular, guanylate cyclase is a heat-stable enterotoxin causing Yersinia-associated diarrhea, and RTX-like toxins are responsible for attachment to integrin on the target cell for cytotoxic action. This genome can be used to identify virulence factors that can be applied for the development of novel biomarkers for the rapid detection of this pathogen in foods.