• Journal of Microbiology and Biotechnology
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• v.28 no.6
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• pp.849-859
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• 2018

Herpes simplex virus type 2 (HSV-2) infection has been a public health concern worldwide. It is the leading cause of genital herpes and a contributing factor to cervical cancer and human immunodeficiency virus (HIV) infection. No vaccine is available yet for the treatment of HSV-2 infection, and routinely used synthetic nucleoside analogs have led to the emergence of drug resistance. The small molecule $Retro-2^{cycl}$ has been reported to be active against several pathogens by acting on intracellular vesicle transport, which also participates in the HSV-2 lifecycle. Here, we showed that Retro-2.1, which is an optimized, more potent derivative of $Retro-2^{cycl}$, could inhibit HSV-2 infection, with 50% inhibitory concentrations of $5.58{\mu}M$ and $6.35{\mu}M$ in cytopathic effect inhibition and plaque reduction assays, respectively. The cytotoxicity of Retro-2.1 was relatively low, with a 50% cytotoxicity concentration of $116.5{\mu}M$. We also preliminarily identified that Retro-2.1 exerted the antiviral effect against HSV-2 by a dual mechanism of action on virus entry and late stages of infection. Therefore, our study for the first time demonstrated Retro-2.1 as an effective antiviral agent against HSV-2 in vitro with targets distinct from those of nucleoside analogs.

• Journal of Korean Academy of Oral and Maxillofacial Radiology
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• v.27 no.2
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• pp.91-103
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• 1997

The purpose of this study was to aid in the prediction of tumor cell tolerance to radiotherapy and/or chemotherapy. For this study, cell surviving curves were obtained for human epidermoid carcinoma A-253 cell line using semiautomated MTT assay. 2,4,6,8,10 Gy were irradiated at a dose rate of 210 cGy/min using /sup 60/Co Irradiator ALDORADO 8. After irradiation, A-253 cell lines(2×10⁴cells/mil were exposed to bleomycin or cisplatin for 1 hour. The viable cells were determined for each radiation dose with/without 2 /lg/mi of drug at the 3rd day. And they were compared to control values. The results were obtained as follows : 1. The surviving curve with gentle slope was obtained after irradiation of 2, 4, 6, 8, 10 Gy on A-253 cell line. 2. The cytotoxicity of bleomycin or cisplatin at the concentration of 2㎍/ml was great on A-253 cell line. But, there was no significant difference between the cytotoxicity of bleomycin and that of cisplatin. 3. There were significant differences of surviving fractions after irradiation with 2㎍/mi of bleomycin compared with irradiation only on A-253 cell line. 4. There were significant differences of surviving fractions after irradiation with 2㎍/ml of cisplatin compared with irradiation only on A-253 cell line. 5. There were no significant differences of surviving fractions between the groups of irradiation with bleomycin and the groups of irradiation with cisplatin on A-253 cell line.

• Korean Journal of Medicinal Crop Science
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• v.14 no.2
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• pp.77-81
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• 2006

As a result of cytotoxic compounds against cancer cell lines from natural sources, senven compounds were isolated from the leaf and twig of Acer okamotoanum Nakai. The compounds (1-7) were identified as ethyl gallate (1), methyl gallate (2), gallic acid (3), trans $resveratrol-3-O-{\beta}-D-glucopyranoside$ (4), acertannin (5), nikoenoside (6), and fraxin (7) by physicochemical and spectroscopic data (including mp, UV, IR, MS, $^1H-NMR,\;^{13}C-NMR$, DEPT, and HMBC) in comparison with those of published papers. All the compounds were tested for their cytotoxic activity against L1210, HL-60, K562, and B16F10 cancer cell lines in vitro by MTT assay method. Compounds 1-3 and 5 showed cytotoxic activity against all tested cell lines with $IC_{50}$ values ranged from 12.5 to $72.2\;{\mu}M$. Of the compounds, methyl gallate (2) exhibited the most potent cytotoxic activity against L1210, HL-60, K562, and B16F10 tumor cells with $IC_{50}$ values of 12.5, 48.3, 22.8, and $22.8\;{\mu}M$, respectively. Other compounds did not show any cytotoxic activity against four cancer cell lines.

• Journal of Korean Academy of Oral and Maxillofacial Radiology
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• v.27 no.1
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• pp.43-53
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• 1997

The purpose of this study was to aid in the prediction of tumor cell tolerance to radiotherapy and/or chemotherapy. For this study, cell surviving curves were obtained for mouse lymphoma YAC-1 cell line using semi automated MTT assay. 2, 4,6, 8, 10Gy were irradiated at a dose rate of 210cGy/rnin using /sup 60/Co Irradiator ALDORADO 8. After irradiation, YAC-1 cell lines(3×10⁴cells/ml) were exposed to bleomycin or cisplatin for 1 hour. The viable cells were determined for each radiation dose and/or each concentration of drug at the 4th day. And they were compared to control values. The obtained results were as follows : 1. The surviving curve with gentle slope was obtained after irradiation of 2, 4, 6, 8, 10 Gy on YAC-1 cell line. 2. The cytotoxicity of bleomycin or cisplatin was increased significantly at all concentration of 0.2㎍/ml, 2㎍/ml and 20㎍/ml on YAC-1 cell line (P<0.01). And the cytotoxicity of cisplatin was greater than that of bleomycin at all concentration on YAC-1 cell line (P<0.01). 3. There were no significant differences of surviving fractions among 4Gy, 6Gy and 8Gy after irradiation of each radiation dose with 2㎍/ml of bleomycin compared with irradiation only on YAC-1 cell line. 4. There was significant difference of surviving fraction between 2Gy and 10Gy after irradiation of each radiation dose with 2㎍/ml of cisplatin compared with irradiation only on YAC-1 cell line(P<0.05). 5. There were significant differences of surviving fractions between the groups of irradiation only and the groups of irradiation with 2㎍/ml of bleomycin or cisplatin at all doses of 2, 4, 6, 8 and 10Gy on YAC-1 cell line(P<0.05).

• Archives of Pharmacal Research
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• v.16 no.3
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• pp.219-226
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• 1993

For the analysis of structure relationship of ar-turmerone analogues, the compounds containing the various substituents on the phenyl ring and 1(or 2)-naphthyl group in the place of phenyl of ar-turmerone were prepared and tested their cytotoxicity against HL-60, K-562, and L1210 leukemia cells in vitro. The substituents at para position are methoxy, phenoxy, methyl, trifluoromethyl, fluoro, and chloro. At meta position methoxy, methyl, trifluoromethyl, or chloro groups at ortho position mathoxy or chloro group were introduced. Against HL-60 and K-562 cells, $ED_{50}$ values of the analogues are ranged from 0.8 to $30.0\;\mu{g/ml}$. Againste L1210 cell, these are located more than $20.0\;\mu{g/ml}$. However, 5-carbone-thoxy-2-methyl-6(1-naphthyl)-2-octen-4-one (5n)possesses $ED_{50}$ valuses 0.8, 2.1, $6.5\;\mu{g/ml}$ against HL-60, L1210 cells, respectively. The electronic nature of the substituents on phenyl ring of ar-tumerone dose not affect the biological activity. Therefore the flat structure of aromatic potion of ar-tumerone analogues is the more important factor for their activity rather than its electronic nature. The potentiation of the cytotoxicity with the enlargement of aromatic ring region also supports the importance of the plane structure of this area. The restriction of the single bond rotation between C-6 and aromatic ring through the introduction of substituents at the ortho position of phenyl ring and the increment of size of alkyl group at C-6 position enhances the activity. Therefore the effective conformation should by the one having the orthogonal arrangement between the aromatic ring and the side chain.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.19 no.3
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• pp.287-299
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• 1997

Procurement, cutting, cleansing, freezing, freeze-drying, and demineralization of the allogeneic bone must be made under the germ-free stable condition without bacterial and/or viral contamination. Even thought the bone is procured under the germ free condition, we must have confidence on disinfection of all the solutions that come in contact with tissue during the whole procedure. Lots of antibacterial agents have been introduced for chemical sterilization. Recently ethylene oxide gas sterilization or radiation sterilization is frequently selected as a secendary sterilization procedure. The biological and biochemical response of the graft material differs with the type and concentration of the sterilizing agents, and various toxic reactions have been reported due to the graft material itself and the substance released by the chemicals. The authors conducted the Millipore filter test to observe the toxic effect on L929 fibroblasts according to the effect on activity of succinate dehydrogenase, during the secondary sterilization of the demineralized allogeneic bone powder with irradiation or ethylene oxide gas. The result were as follows : 1. Around the copper disk, positive control group, 10mm diameter discoloration was observed. 2. As same as the negative control group, the disk showed no discoloration. 3. The demineralized allogeneic bone which was sterilized with ethylene oxide gas or irradiation showed no cytotoxicity. 4. From this results, it is suggested that treatment with ethylene oxide gas or irradiation should be effective to sterilize the deminineralized allogeneic bone.

• Bulletin of the Korean Chemical Society
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• v.29 no.7
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• pp.1303-1310
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• 2008

Inhibitors of farnesyltransferase (FT), a key enzyme in the post-translational modifications of Ras proteins, have been extensively studied as novel anticancer agents in the preclinical stages, some of which are currently in clinical development. Previously, it has been reported that a novel FT inhibitor LB42907 inhibits Ras farnesylation in the nanomolar range in vitro. The aim of this study was to assess the antitumor efficacy of LB42907 in vitro and in vivo. Anchorage-independent growth of various human tumor cell lines was potently inhibited by treatment with LB42907, comparable to other FT inhibitors in clinical development. In the nude mouse, oral administration of LB42907 demonstrated potent antitumor activity in several human tumor xenograft models including bladder, lung and pancreas origin. Interestingly, significant tumor regression in EJ (bladder) and A549 (lung) xenografts was induced by LB42907 treatment. The effectiveness of LB42907 was also investigated in simultaneous combination with paclitaxel, vincristine, cisplatin or gemcitabine against NCI-H460, A549, and HCT116 cells in vitro using median-effect analysis. LB42907 markedly synergized with most anticancer drugs tested in this study in NCI-H460 cell. In contrast, LB42907 displayed antagonism or partial synergism with these drugs in A549 and HCT116 cells, depending on the class of combined drugs and/ or the level of cytotoxicity. Our results demonstrate that LB42907 is an effective antitumor agent in vitro and in vivo and combination of LB42907 with other chemotherapeutic drugs results in synergistic or antagonistic effects mainly in a cell line-dependent manner. Further preclinical study is warranted.

• The Journal of Pediatrics of Korean Medicine
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• v.28 no.2
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• pp.56-71
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• 2014

Objectives In this study, the author tried to investigate whether piryongbang-gamgil-tang (PGGT) significantly affect in vitro airway mucin secretion, PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production / gene expression from human airway epithelial cells and increase in airway epithelial mucosubstances and hyperplasia of tracheal goblet cells of rats. Materials and Methods For in vitro experiment, confluent RTSE cells were chased for 30 min in the presence of PGGT to assess the effect of PGGT on mucin secretion by enzyme-linked immunosorbent assay (ELISA). Also, effect of PGGT on PMA- or EGFor TNF-${\alpha}$-induced MUC5AC mucin production and gene expression from human airway epithelial cells (NCI-H292) were investigated. Confluent NCI-H292 cells were pretreated for 30 min in the presence of PGGT and treated with PMA (10 ng/ml) or EGF (25 ng/ml) or TNF-${\alpha}$ (0.2 nM) for 24 hrs, to assess both effect of PGGT on PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production by ELISA and gene expression by reverse transcription-polymerase chain reaction (RT-PCR). For in vivo experiment, the author induced hypersecretion of airway mucus and goblet cell hyperplasia by exposure of rats to $SO_2$ during 3 weeks. Effect of orally-administered PGGT during 2 weeks on increase in airway epithelial mucosubstances from tracheal goblet cells of rats and hyperplasia of goblet cells were assesed by using histopathological analysis after staining the epithelial tissue with alcian blue. Possible cytotoxicities of PGGT in vitro were assessed by examining LDH release from RTSE cells and the rate of survival and proliferation of NCI-H292 cells. In vivo liver and kidney toxicities of PGGT were evaluated by measuring serum GOT/GPT activities and serum BUN/creatinine concentrations of rats after administering PGGT orally. Results (1) PGGT did not affect in vitro mucin secretion from cultured RTSE cells. (2) PGGT significantly inhibited PMA-, EGF-, and TNF-${\alpha}$-induced MUC5AC mucin productions and the expression levels of MUC5AC mRNA from NCI-H292 cells. (3) PGGT decreased the amount of intraepithelial mucosubstances and showed the tendency of expectorating airway mucus already produced. (4) PGGT increased LDH release from RTSE cells. However, PGGT did not show in vivo liver and kidney toxicities and cytotoxicity to NCI-H292 cells. Conclusion The result from this study suggests that PGGT can regulate the production and gene expression of airway mucin observed in diverse respiratory diseases accompanied by mucus hypersecretion and do not show in vivo toxicity to liver and kidney functions after oral administration. Effect of PGGT with their components should be further studied using animal experimental models that reflect the diverse pathophysiology of respiratory diseases through future investigations.

• Biomolecules & Therapeutics
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• v.28 no.5
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• pp.456-464
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• 2020

Mast cells (MCs) are systemically distributed and secrete several allergic mediators such as histamine and leukotrienes to cause type I hypersensitivity. Dasatinib is a type of anti-cancer agent and it has also been reported to inhibit human basophils. However, dasatinib has not been reported for its inhibitory effects on MCs or type I hypersensitivity in mice. In this study, we examined the inhibitory effect of dasatinib on MCs and MC-mediated allergic response in vitro and in vivo. In vitro, dasatinib inhibited the degranulation of MCs by antigen stimulation in a dose-dependent manner (IC₅₀, ~34 nM for RBL-2H3 cells; ~52 nM for BMMCs) without any cytotoxicity. It also suppressed the secretion of inflammatory cytokines IL-4 and TNF-α by antigen stimulation. Furthermore, dasatinib inhibited MC-mediated passive cutaneous anaphylaxis (PCA) in mice (ED₅₀, ~29 mg/kg). Notably, dasatinib significantly suppressed the degranulation of MCs in the ear tissue. As the mechanism of its effect, dasatinib inhibited the activation of Syk and Syk-mediated downstream signaling proteins, LAT, PLCγ1, and three typical MAP kinases (Erk1/2, JNK, and p38), which are essential for the activation of MCs. Interestingly, in vitro tyrosine kinase assay, dasatinib directly inhibited the activities of Lyn and Fyn, the upstream tyrosine kinases of Syk in MCs. Taken together, dasatinib suppresses MCs and PCA in vitro and in vivo through the inhibition of Lyn and Fyn Src-family kinases. Therefore, we suggest the possibility of repositioning the anti-cancer drug dasatinib as a treatment for various MC-mediated type I hypersensitive diseases.

• The Journal of Internal Korean Medicine
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• v.29 no.2
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• pp.318-333
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• 2008

Objectives : In this study, the author tried to examine whether Cheogjogupye-tang (淸燥救肺湯, CGPT) and Yieum-jeon (理陰煎, YEJ) significantly affect in vitro and in vivo mucin secretion, MUC5AC gene expression in airway epithelial cells and contractility of isolated tracheal smooth muscle of rabbit. Materials and Methods : For in vitro experiment, confluent hamster tracheal surface epithelial (HTSE) cells were chased for 30 minutes in the presence of CGPT and YEJ to assess the effects of the agents on mucin secretion by enzyme-linked immunosorbent assay (ELISA), with removal of oriental herbal medicine extract from each agent-treated sample by centrifuge microfilter. Also, the effects of the agents on TNF-alpha or EGF-induced MUC5AC gene expression in human airway epithelial cells (NCI-H292) were investigated. Possible cytotoxicities of the agent were assessed by examining both LDH release from HTSE cells and the rate of survival and proliferation of NCI-H292 cells. For in vivo experiment, hypersecretion of airway mucin and goblet cell hyperplasia was induced by exposure of rats to $SO_2$ over 3 weeks. Effects of CGPT and YEJ orally administered for 1 week on in vivo mucin secretion from tracheal goblet cells of rats and hyperplasia of goblet cells were assessed using ELISA and histological analysis after staining the epithelial tissue with alcian blue, respectively. Also, the effects of CGPT and YEJ on contractility of isolated tracheal smooth muscle were investigated. Results : (1) CGPT significantly inhibited in vitro mucin secretion from cultured HTSE cells. However, YEJ did not affect in vitro mucin secretion; (2) CGPT and YEJ did not affect hypersecretion of in vivo mucin and hyperplasia of tracheal goblet cells; (3) CGPT and YEJ slightly increased the expression levels of TNF-alpha or EGF-induced MUC5AC gene in NCI-H292 cells; (4) CGPT and YEJ inhibited acetylcholine-induced contraction of isolated tracheal smooth muscle of rabbit; (5) CGPT and YEJ did not affect LDH release from HTSE cells and the survival and proliferation of NCI-H292 cells. Conclusion : The results from the present study suggest that CGPT and YEJ mainly affect the expression of mucin gene rather than secretion of mucin and do not show remarkable cytotoxicity to respiratory epithelial cells.