• Journal of Oral Medicine and Pain
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• v.36 no.1
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• pp.11-20
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• 2011

Valproic acid (VPA) is a well-known anticonvulsive agent and has been used in the treatment of epilepsy for almost 30 years. VPA emerged in 1997 as an antineoplastic agent. And it is known that antitmor activity of VPA is associated with its targeted at histone deacetylases. 17AAG, Inhibition of HSP90 leads to the proteasome degradation of the HSP90 client proteins, such as Akt, Raf/Ras, Erk, VEGF, cyclin D and p53, and causes potent antitumor activity. It is reported that 17AAG-induced HSP90 inhibition results in prevention of cell proliferation and induction of apoptosis in several types of cancer. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with the histone deacetylases inhibitor, VPA and the HSP90 inhibitor, 17AAG on human osteosarcoma (HOS) cells. Cell viability was evaluated by trypan-blue exclusion. Induction and augmentation of apoptosis were confirmed by Hoechst staining, flow cytometry (DNA hypoploidy and MMP change), Westen blot analysis and immunofluorescent staining. In this study, HOS cells co-treated with VPA and 17AAG showed several lines of apoptotic manifestation such as nuclear condensations, the reduction of MMP, the decrease of DNA content, the release of cytochrome c into cytosol, the translocation of AIF onto nuclei, and activation of caspase-3, caspase-7 and PARP whereas each single treated HOS cells did not. Although the single treatment of 1 mM VPA or 0.5 ${\mu}M$ 17AAG for 48 h did not induce apoptosis, the co-treatment with them induced prominently apoptosis. Therefore our data in this study provide the possibility that combination therapy with VPA and 17AAG could be considered as a novel therapeutic strategy for human osteosarcoma.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.5
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• pp.515-520
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• 2007

This study was peformed to determine the antioxidative, antimutagenic and cytotoxic effects of the natural seasoning using Lentinus edodes powder (NSLP) by DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical donating method, Ames test, and cytotoxicity, respectively. The scavenging effect on DPPH radical in ethyl acetate fraction of NSLP showed $155{\mu}g\;of\;RC_{50}$. The direct antimutagenic effects of ethanol extract and its solvent fractions of NSLP were examined by Ames test using Salmonella Typhimurium TA98 and TA100. In the Ames test, ethanol extract of NSLP alone did not exhibit any mutagenicity and most of the samples showed high antimutagenic effects against mutation induced by N-methyl-N'-nitro-N-nitroso guanidine (MNNG) and 4-nitroquinoline-1-oxide (4NQO). Ethyl acetate fraction of NSLP ($200{\mu}g/plate$) showed approximately 82% inhibitory effect on the mutagenesis induced by 4NQO against TA98 strain, whereas 84% and 80% inhibitions were observed on the mutagenesis induced by 4NQO and MNNG against TA100 strain. In anticancer effects of ethanol extract and its solvent fractions of NSLP against cancer cell lines including human lung carcinoma (A549), human breast adenocarcinoma (MCF-7), human hepatocellular carcinoma (Hep3B), human cervical adenocarcinoma (HeLa) and human gastric carcinoma (AGS) were investigated. The treatment of 1 mg/mL ethyl acetate fraction of NSLP showed strong cytotoxicity of 56.7%, 84.9%, 64.6%, 85.1% and 71.5% against A549, MCF-7, Hep3B, HeLa and AGS, respectively. In contrast 1 mg/mL treatment of NSLP extract and its solvent fractions had only $4{\sim}40%$ cytotoxicity on human transfomed primary embryonal kidney cell (293). From this result, it is suggested that NSLP is believed to have possible antioxidative, antimutagenic and anticancer capacities.

• Journal of Life Science
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• v.25 no.1
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• pp.53-61
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• 2015

In this study, we tried to separate the photosensitizer that induces apoptosis of leukemia cells (U937) from perilla leaves. Perilla leaves (Perilla frutescens Britt var. japonica Hara) are a popular vegetable in Korea, being rich in vitamins (A and E), GABA, and minerals. Dried perilla leaves were extracted with methanol to separate the photosensitizer by various chromatographic techniques. The structure of the isolated compound (PL9443) was identified by 1D-NMR, 2D-NMR, and FAB-mass spectroscopy. Absorbance of the UV-Vis spectrum was highest at 410 nm and was confirmed by the 330, 410, and 668 nm. PL9443 compound was determined to be pheophorbide, an ethyl ester having a molecular weight of 620. It was identified as a derivative compound of pheophorbide structure when magnesium comes away from a porphyrin ring. Observation of morphological changes in U937 cells following cell death induced by treated PL9443 compound revealed representative phenomena of apoptosis only in light irradiation conditions (apoptotic body, vesicle formation). Results from examining the cytotoxicity of PL9443 substance against U937 cells showed that inhibition rates of the cell growth were 99.9% with the concentration of 0.32 nM PL9443. Also, the caspase-3/7 activity was 99% against U937 cells with the concentration of 0.08 nM of PL9443 substance. The result of the electrophoresis was that a DNA ladder was formed by the PL9443. The PL9443 compound is a promising lead compound as a photosensitizer for photodynamic therapy of cancer.

• Korean Journal of Medicinal Crop Science
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• v.10 no.2
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• pp.132-138
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• 2002

This study was performed to determine the antimutagenic and cytotoxic effect of ,Kalopanacis cortex endothelium. Methanol extract was used on Salmonella typhimurium TA98, TA100 and three cancer cell lines. In the Ames test, methanol extract of Kalopanacis cortex endothelium alone did not exhibit any mutagenicity but showed substantial inhibitory effects against mutation induced by 4-nitroquinoline-l-oxide(4NQO), N'-methyl- N'-nitro-N-nitrosoguanidine(MNNG) and benzo(a)pyrene(B(a)P). The methanol extract of Kalopanacis cortex endothelium showed approximately 79.29% and 75.38% inhibitory effect on the mutagenesis induced by 4NQO and B(a)P, respectively, against TA98 strain. Whereas 79.49%, 89.3% and 68.85% inhibitions were observed on the mutagenesis induced by 4NQO, MNNG and B(a)P against TA100 strain. Methanol extracts from Kalopanacis cortex endothelium showed high antimutagenic effects against 4NQO, MNNG and B(a)P. The anticancer effects of methanol extract from Kalopanacis cortex endothelium against human lung carcinoma(A549), human breast adenocarcinoma (MCF-7) and human hepatocellular carcinoma(Hep3B) were investigated. The treatment of 0.5mg/ml Kalopanacis cortex endothelium methanol extracts had the highest cytotoxicity against A549(81.54%), followed by MCF-7(81.92%) and Hep3B (78.57%). In contrast 0.5mg/ml treatment of methanol extracts from Kalopanacis cortex endothelium had only $4{\sim}25%$ cytotoxicity on normal human liver cell(293).

• The Journal of the Korean Society for Microbiology
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• v.21 no.4
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• pp.447-453
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• 1986

To diagnose the typhoid fever rapidly and accurately in clinically suspected patients, the levels of IgG subclass antibody were measured by enzyme-linked immunosorbent assay(ELISA). With symptom, blood culture and agglutination test, tested persons were categorized into 6 groups as typhoid fever, FUO, paratyphi A or B, other bacterial infctions, cancers, and control. ELISA was performed on the polyvinyl chloride plates coated with killed whole cell($10^8\;cell/ml$) of S. typhi 0901W by poly-L-lysine applied as binding substance (and polyvinyl chloride as solid phase). The distribution of the level of IgG subclass antibodies in each group was analyzed and compared with other groups. The results obtained were summarized as follow: 1. The optimal dilution of the sera from patients with typhoid fever was 1:160, and those of the sheep anti-human IgG subclass and the peroxidase conjugated rabbit anti-sheep IgG were 1:4000 and 1:5000, respectively. 2. The absorbance levels of IgG subclass in the sera of typhoid fever patients were as follows; a) IgG1 value is $0.439{\pm}0.110$ b) IgG2 value is $0.416{\pm}0.165$ c) IgG3 value is $0.449{\pm}0.145$ d) IgG4 value is $0.525{\pm}0.154$ IgG subclass levels in the sera of typhoid patients were much higher than in control group and patient with paratyphi A or B as well as other infectious diseases. The sensitivity and the specificity in differential diagnosis of typhoid fever and other febrile diseases were 92% and 79% in the assay of IgG1 respectively, whereas those in the assay of IgG2 were 97% and 72%, respectively (above absorbance 0.3). 3. The absorbance levels of IgG subclass in the serial sera of typhiod fever patients tend to decrease to the level of absorbance 0.3 in 10 months from the onset of illness. 4. The order of absorbance levels of IgG subclass in the serum of each group were typhoid fever, paratyphi A or B, other infectious diseases, control and cancer. 5. For the serodiagnosis of typhoid fever against other febrile diseases, the sensitivity and the specificity in the assay of IgG2 activity were 76% and 93% in absorbance 0.4, respectively. 6. In the distribution of the level of each IgG subclass in the sera of FUO patients which were suspected of typhoid fever, the positive rate was ranged from 36% to 82%. This suggest that more than 50% of FUO patients are caused by S. typhi.

• Journal of Life Science
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• v.26 no.1
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• pp.23-33
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• 2016

Pexa-Vec (JX-594) is a specific cancer-targeted oncolytic and immunotherapeutic vaccinia virus. The purpose of this study was to develop methods to maximize the stability of Pexa-Vec. In short-term instability testing, viral activity was rapidly decreased both at 4℃ and at room temperature (RT), but it was completely restored after sonication followed by vortex. Long-term stability testing of Pexa-Vec in the following liquid formulations was performed: (A) 30 mM Tris/pH 7.6, (B) 30 mM Tris/pH 8.6, (C) 30 mM Tris/pH 7.6, 150 mM NaCl, 15% sucrose, (D) 30 mM Tris/pH 7.6, 15% sucrose, and (E) 30 mM Tris/pH 8.6, 15% sucrose. Viral activity decreased less than 2 log10 at 4℃, and RT was observed in 3 days in B, while viral activity was not decreased even after 4–8 weeks at 4℃ and at 1 week in RT in A, suggesting that neutral pH may be essential to maintain virus stability. The addition of 15% sucrose into A (D) significantly increased viral stability at −20℃, 4℃, or RT, and it was also observed at pH 8.6 (E). The addition of 150 mM NaCl into D (C) significantly increased viral stability in addition to the sucrose effect at 4℃ or RT. Accordingly, the viral activity in formulation C was maintained for 1.5 years at 4℃, and for 1-2 weeks in RT. In conclusion, we propose that formulation C can provide the most adequate condition for the proper storage of vaccinia oncolytic virus.

• Food Science and Preservation
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• v.11 no.4
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• pp.550-556
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• 2004

In the present study, we investigated the antimutagenic and cytotoxic effects of Acer ginnala Max. bark extract on S. typhimurium TA98, TA100 and cancer cell lines with Ames test and SRB assay, respectively. They were extracted with methanol and then fractionated using hexane, chloroform, ethyl acetate, butanol, and water to obtain the fractions. The inhibition rate of methanol ($200\;{\mu}g/plate$) of Acer ginnala Max. bark extract in the Salmonella typhimurium TA100 strain showed $83.3\%$ against the mutagenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). In addition, the suppression of methanol extract with same concentration of in the Salmonella typhimurium TA98 and TA100 strains showed $80.3\%\;and\;92.7\%$ inhibition against 3-amino-1,4-dimethyl-5H-pyrido-(4,3-b)indol (Trp-P-1), respectively. The cytotoxicity effects of Acer ginnala Max. bark extract against the cell lines with human lung carcinoma (A549), human gastric carcinoma (AGS), human hepatocellular carcinoma (Hep3B) and human breast adenocarcinoma (MCF-7) were inhibited with the increase of the extract concentration. The treatment of 1.0 mg/mL Acer ginnala Max. bark methanol extract of methanol showed strong cytotoxicities of $77.3\%,\;90.4\%,\;88.9\%,\;and\;83.7\%$ against A549, AGS, Hep3B and MCF-7, respectively.

• Journal of Life Science
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• v.18 no.1
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• pp.16-22
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• 2008

In this study to evaluate the involvement of EGFR, HER-2/neu and ALCAM (CD166) oncogene products in canine mammary neoplastic lesions, sections of archived paraffin-embedded samples of 49 mammary tumors were analyzed immunohistochemically using antibodies against human EGFR and HER-2/neu and ALCAM. These 49 tumors were divided into 2 groups: 22 benign (19 adenoma, 3 benign mixed tumors) and 27 malignant tumors (2 simple adenocarcinomas, 5 complex adenocarcinomas, 3 solid carcinoma, 5 sclerosing carcinoma, 8 malignant mixed tumors and 4 malignant myoepithelioma). As a result of immunostaining, 31.8% (7/22) of the benign tumors and 29.6% (8/27) of the malignant tumors expressed the HER-2/neu oncogene product, EGFR expression was detected in 27.3% (6/22) of benign tumors and in 22.2% (6/27) of the malignant tumors. ALCAM expression was detected in 40.9% (9/22) of benign tumors and in 7.4% (2/27) of the malignant tumors. These results suggest that some of the biological and morphological characteristics of the tumor are associated with canine mammary gland tumors, as also reported for human breast cancer, the possibility of using anti-HER-2/neu antibodies in the treatment of canine mammary tumors.

• Journal of Life Science
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• v.23 no.4
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• pp.501-509
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• 2013

Formaldehyde (FA) is widely used in industries, and it is an indoor and outdoor pollutant. Exposure to FA may cause inflammation and respiratory oxidative stress. Studies have demonstrated that FA can cause cancer in animal models. During the regeneration process of injured starfish (Asterina pectinifera), several changes have been observed in the expression of cytokines. In particular, higher TGF-${\beta}1$ expression has been detected in arm cut starfish extract after eight days. The current study was designed to elucidate the in-vitro and the in-vivo pharmacological effects of starfish extract on FA exposure. We investigated the protective effects of intact starfish extract and arm cut starfish extract on an IMR-90 cell line and on mouse lung injury in response to FA exposure. In the presence of FA, inhalation of the arm cut starfish extract was associated with more promising cell proliferation, TNF-${\alpha}$, NF-${\kappa}B$ decrement, and $I{\kappa}-B{\alpha}$ increment. In the experimental group, the pulmonary structure of the arm cut starfish extract-treated group in the presence of FA exposure was similar to the control group, whereas the FA exposure group showed damage to the pulmonary structure. Moreover, the arm cut starfish extracts was more effective than the intact starfish extracts in terms of the expression of TNF-${\alpha}$, NF-${\kappa}B$, $I{\kappa}-B{\alpha}$, and surfactant protein A. The results obtained in this study demonstrate that arm cut starfish extracts are more effective in protecting pulmonary structure and function against FA exposure than intact starfish extracts.

• Journal of Life Science
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• v.30 no.11
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• pp.931-938
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• 2020

Translationally controlled tumor protein (TCTP) is one of the most abundant proteins in various eukaryotic organisms. TCTPs play important roles in cell physiological processes in cancer, cell proliferation, gene regulation, and heat shock response. TCTP is also considered an important factor in the resistance to oxidative stress induced by dithiothreitol or hydrogen peroxide (H₂O₂). Arctic calanoid copepods have a variety of antioxidant defense systems to regulate the levels of potentially harmful reactive oxygen species generated by ultraviolet radiation in the Arctic marine ecosystem. However, information on the antioxidant activity of TCTP in the Arctic Calanus glacialis is still scarce. To understand the putative antioxidant function of the Arctic copepod C. glacialis TCTP (Cg-TCTP), its gene was cloned and sequenced. The Cg-TCTP comprised 522 bp and encoded a 174-amino acid putative protein with a calculated molecular weight of ~23 kDa. The recombinant Cg-TCTP (Cg-r TCTP) gene was overexpressed in Escherichia coli (BL21), and Cg-rTCTP-transformed cells were grown in the presence or absence of H₂O₂. Cg-rTCTP-transformed E. coli showed increased tolerance to high H₂O₂ concentrations. Therefore, TCTP may be an important antioxidant protein related to tolerance of the Arctic copepod C. glacialis to oxidative stress in the harsh environment of the Arctic Ocean.