• Title/Summary/Keyword: Cytotoxic ability

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Molecular Characterization of the Recombinant A-chain of a Type II Ribosome-Inactivating Protein (RIP) from Viscum album coloratum and Structural Basis on its Ribosome-Inactivating Activity and the Sugar-binding Properties of the B-chain

  • Ye, Wenhui;Nanga, Ravi Prakash Reddy;Kang, Cong Bao;Song, Joo-Hye;Song, Seong-Kyu;Yoon, Ho-Sup
    • BMB Reports
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    • v.39 no.5
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    • pp.560-570
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    • 2006
  • Mistletoe (Viscum album) lectins, which are classified as a type II ribosome-inactivating protein (RIP) due to their unique biological function and the potential medical and therapeutic application in cancer cells, receive a rising attention. The heterodimeric glycoproteins contain the A-chain with catalytic activity and the B-chain with sugar binding properties. In recent years, studies involving the lectins from the white berry European mistletoe (Viscum album) and the yellow berry Korean mistletoe (Viscum album coloratum) have been described. However, the detailed mechanism in exerting unique cytotoxic effect on cancer cells still remains unclear. Here, we aim to understand and define the molecular basis and biological effects of the type II RIPs, through the studies of the recombinant Korean mistletoe lectin. To this end, we expressed, purified the recombinant Korean mistletoe lectin (rKML), and investigated its molecular characteristics in vitro, its cytotoxicity and ability to induce apoptotic cell death in cancer cells. To gain structural basis for its catalytic activity and sugar binding properties, we performed homology modeling studies based on the high degree of sequence identity and conserved secondary structure prediction between Korean and European, Himalayan mistletoe lectins, and Ricin.

Immunotherapeutic Effects of Dendritic Cells Pulsed with a Coden-optimized HPV 16 E6 and E7 Fusion Gene in Vivo and in Vitro

  • Zhou, Zhi-Xiang;Li, Dan;Guan, Shan-Shan;Zhao, Chen;Li, Ze-Lin;Zeng, Yi
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.9
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    • pp.3843-3847
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    • 2015
  • Background: Cervical cancer is the second most common cause of cancer related death of women. Persistent HPV infection, especially with high-risk types such as HPV16 and HPV18, has been identified to be the primary cause of cervical cancer. E6 and E7 are the major oncoproteins of high-risk HPVs, which are expressed exclusively in HPV infected tissues, and thereby represent ideal therapeutic targets for immunotherapy of cervical cancer. Materials and Methods: In this work, we used recombinant adenovirus expressing coden-optimized HPV16 E6 and E7 fusion protein (Ad-ofE6E7) to prime dendritic cells (DC-ofE6E7), to investigate the ability of primed DC vaccine in eliciting antitumor immunity in vitro and vivo. Results: Our results indicated that DC-ofE6E7 vaccine co-culturing with splenocytes could strongly induce a tumor-specific cytotoxic T lymphocyte (CTL) response and kill the TC-1 cells effectively in vitro. Moreover, DC-ofE6E7 vaccine induced protective immunity against the challenge of TC-1 cancer cells in vivo. Conclusions: The results suggested that the HPV16 ofE6E7 primed DC vaccine has potential application for cervical cancer immunotherapy.

Sequential Conjugation of 6-Aminohexanoic Acids and L-Arginines to Poly(amidoamine) Dendrimer to Modify Hydrophobicity and Flexibility of the Polymeric Gene Carrier

  • Yu, Gwang-Sig;Yu, Ha-Na;Choe, Yun-Hui;Son, Sang-Jae;Ha, Tai-Hwan;Choi, Joon-Sig
    • Bulletin of the Korean Chemical Society
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    • v.32 no.2
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    • pp.651-655
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    • 2011
  • We synthesized a novel cationic dendrimer consisting of a poly(amidoamine) dendrimer (PAMAM, generation 4) backbone with both L-arginine (Arg) at the termini and 6-aminohexanoic acid (Ahx) between the original core polymer and the peripheral Arg units. The sequential chemical modification of PAMAM G4 with Ahx and Arg resulted in higher transfection efficiency with much less cytotoxicity. PAMAM G4-Ahx-Arg formed stable polyplexes at weight ratios of 8:1 or higher (polymer: plasmid DNA), and the mean polyplex diameter was $180{\pm}20nm$. PAMAM G4-Ahx-Arg showed much higher transfection ability than PAMAM G4 or PAMAM G4-Ahx. Furthermore, PAMAM G4-Ahx-Arg was much less cytotoxic than PEI25KD and PAMAM G4-Arg. In addition to Arg grafting of the PAMAM dendrimer, which endows a higher transfection capability, the addition of Ahx spacer increased dendrimer hydrophobicity, introduced flexibility into the conjugated amino acids, and reduced cytotoxicity. Overall, it appears that the concomitant modification of PAMAM with Ahx and Arg could lead to new PAMAM conjugates with better performances.

Strobilanthes crispus Juice Concentrations and Anticancer Effects on DNA Damage, Apoptosis and Gene Expression in Hepatocellular Carcinoma Cells

  • Hussin, Faridah;Eshkoor, Sima Ataollahi;Rahmat, Asmah;Othman, Fauziah;Akim, Abdah;Eshak, Zolkapli
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.6047-6053
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    • 2015
  • Background: Hepatocellular carcinoma is one of the most common cancers worldwide. Its prevalence is increasing in many countries. Plant products can be used to protect against cancer due to natural anticancer and chemopreventive constituents. Strobilanthes crispus is one of plants with potential chemopreventive ability. Objective: This study aimed to evaluate the anticancer effects of Strobilanthes crispus juice on hepatocellular carcinoma cells. Materials and Methods: MTT assays, flow cytometry, comet assays and the reverse transcription-polymerase chain reaction (RT-PCR) were used to determine the effects of juice on DNA damage and cancer cell numbers. Results: This juice induced apoptosis after exposure of the HepG2 cell line for 72 h. High percentages of apoptotic cell death and DNA damage were seen at the juice concentrations above 0.1%. It was found that the juice was not toxic for normal cells. In addition, juice exposure increased the expression level of c-myc gene and reduced the expression level of c-fos and c-erbB2 genes in HepG2 cells. The cytotoxic effects of juice on abnormal cells were in dose dependent. Conclusions: It was concluded that the Strobilanthes crispus juice may have chemopreventive effects on hepatocellular carcinoma cells.

Effect of Samultanggamibang of Apoptosis of Melanoma cell (사물탕(四物湯) 가미방(加味方)이 흑색중(黑色腫) 세포고사(細胞枯死)에 미치는 효과(效果))

  • Park, Eun-Jung;Lee, Hai-Ja;Chang, Sung-Jin
    • The Journal of Pediatrics of Korean Medicine
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    • v.20 no.1
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    • pp.257-272
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    • 2006
  • Objective : In this study, the ability of Oriental medicine Samultanggamibang(SMTG) to induce apoptosis was investigated in B16F10 melanoma cells. Method : Tetrazolium-based colorimetric assay was performed for cytotoxicity test. Several new assays for the basis of biochemical events associated with apoptosis such as DNA fragmentation by a flow cytometry, caspase-3 activation and PARP cleavage by Western blotting should be carried out potentially useful for the basis of biochemical events associated with apoptosis such as a flow cytometry and caspase-3 activation. Results : (1) The number of B16F10 melanoma cells was less than 30 % after exposure to 1 mg/ml SMTG for 48 h. SMTG increased cytotoxicity of B16F10 melanoma cells in a dose- and time-dependent manner. (2) The percentage of apoptotic cells by flow cytometric analysis of the DNA-stained cells increased to 21 % at 24 h and 25 % at 48 h after treatment with 1 mg/ml SMTG. (3) SMTG-induced apoptosis was accompained by the activation of caspase-3 and the specific proteolytic cleavage of poly-ADP-ribose polymerase. (4) SMTG induces the activation of caspase-3 and the specific proteolytic cleavage of poly-ADP-ribose polymearse and eventually leads to apoptosis through c-Jun NH2-terminal protein kinase (JNK)-dependent manner in B16F10 melanoma cells. Conclusion : SMTG had a strong cytotoxic effect of B16F10 melanoma cells.

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Effects of the microbiological properties and pathogenicity of Photobacterium damselae subsp. damselae under different culture conditions (배양 조건이 Photobacterium damselae subsp. damselae의 미생물학적 성상 및 병원성에 미치는 영향)

  • Kwon, Mun-Gyeong;Cho, Byoung-Youl;Park, Myeong-Ae
    • Journal of fish pathology
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    • v.22 no.3
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    • pp.239-251
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    • 2009
  • The effects of microbiological properties and pathogenicity of Photobacterium damselae subsp. damselae were investigated under different culture conditions, temperature, pH, NaCl and iron concentration on culture media. Favorable conditions for bacterial growth were between 15-30${^{\circ}C}$, pH 5-9, 0-4% NaCl concentration and iron contents of over 10 mM, whereas the bacterial growth was inhibited under iron chelator existence. When P. damselae was cultured in iron-limited tryptic soy broth, total protein concentration of extracellular products, cytotoxic ability of ECPs on cell line, bacterial viability in flounder serum, phospholipase and siderophore activities of ECPs were significantly increased. On the other hand, the activities of P. damselae cultured under iron-added conditions were decreased. In this study, the iron-limited conditions were similar to the host in which iron concentration is low. During infection caused by P. damselae, the conditions could be related to the pathogenesis of the pathogen.

Moutan Cortex Radicis contributes to the chemotaxis of eosinophils and secretion of cytokines in A549 human epithelial cells (목단피(牧丹皮)가 천식(喘息)유발 cytokine 분비와 호산구 chemotaxis에 미치는 영향)

  • Moon, Sung-Hun;Jung, Sung-Ki;Rhee, Hyung-Koo;Jung, Hee-Jae
    • The Journal of Internal Korean Medicine
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    • v.26 no.1
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    • pp.199-212
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    • 2005
  • Objective : Airway inflammation is now regarded as a defining feature of asthma. The importance of eosinophits in the airway inflammation of asthma patients is widely recognized, and eosinophils mobilization in the respiratory epithelium is activated by chemoattractants and cytokines. This study was designed to examine the extent of the ability of Moutan Cortex Radicis to inhibit eosinophil chemotaxis of pulmonary epithelium after allergic stimulation. Material and Methods : Water extracts of Moutan Cortex Radicis and pulmonary epithelial cell lines A549(human type II-like epithelial cells) and human eosinophils were used. Cytotoxic effects of Moutan Cortex Radicis were estimated via MTS assay, and the effects of Moutan Cortex Radicis on chemokines from prestimulated A549 cells were estimated by sandwich ELISA and RT-PCR. Chemotaxis assay on prestimulated eosinophils treated with Moutan Cortex Radicis. was conducted Result : In this study we demonstrated that $TNF-{\alpha}$ and IL-4, $IL-1{\beta}$ induced the accumulation of chemokines' mRNA in the pulmonary epithelial cell lines A549 in a dose-dependent manner. Chemokines of eotaxin, ICAM-1, YCAM-1, IL-8, IL-16 were inhibited by Moutan Cortex Radicis in a dose dependent manner, but RANTES showed no inhibition due to Moutan Cortex Radicis. Eosinophil migration was inhibited at high concentrations of Moutan Cortex Radicis. Conculusion : These findings are indicative of supression of chemokines accomplished by Moutan Cortex Radicis treatment, demonstrating the potential therapeutic value of Moutan Cortex Radicis for treating diseases such as asthma.

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Self-Recognition Algorithm of Artificial Immune System (인공면역계의 자기-인식 알고리즘)

  • 심귀보;선상준
    • Journal of the Korean Institute of Intelligent Systems
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    • v.11 no.9
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    • pp.801-806
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    • 2001
  • According as many people use a computer newly, damage of computer virus and hacking is rapidly increasing by the crucial users A computer virus is one of program in computer and has abilities of self reproduction ad destruction like a virus of biology. And hacking is to rob a person's data in a intruded computer and to delete data in a person s computer from the outside. To block hacking that is intrusion of a person s computer and the computer virus that destroys data, a study for intrusion-detection of system and virus detection using a biological immune system is in progress. In this paper, we make a model of positive selection and negative selection of self-recognition process that is ability of T-cytotoxic cell that plays an important part in biological immune system. So we embody a self-nonself distinction algorithm in computer, which is an important part when we detect an infected data by computer virus and a modified data by intrusion from the outside. The composed self-recognition process distinguishes self-file from the changed files. To prove the efficacy of self-recognition algorithm, we use simulation by a cell change and a string change of self file.

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Integration of metabolomics and transcriptomics in nanotoxicity studies

  • Shin, Tae Hwan;Lee, Da Yeon;Lee, Hyeon-Seong;Park, Hyung Jin;Jin, Moon Suk;Paik, Man-Jeong;Manavalan, Balachandran;Mo, Jung-Soon;Lee, Gwang
    • BMB Reports
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    • v.51 no.1
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    • pp.14-20
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    • 2018
  • Biomedical research involving nanoparticles has produced useful products with medical applications. However, the potential toxicity of nanoparticles in biofluids, cells, tissues, and organisms is a major challenge. The '-omics' analyses provide molecular profiles of multifactorial biological systems instead of focusing on a single molecule. The 'omics' approaches are necessary to evaluate nanotoxicity because classical methods for the detection of nanotoxicity have limited ability in detecting miniscule variations within a cell and do not accurately reflect the actual levels of nanotoxicity. In addition, the 'omics' approaches allow analyses of in-depth changes and compensate for the differences associated with high-throughput technologies between actual nanotoxicity and results from traditional cytotoxic evaluations. However, compared with a single omics approach, integrated omics provides precise and sensitive information by integrating complex biological conditions. Thus, these technologies contribute to extended safety evaluations of nanotoxicity and allow the accurate diagnoses of diseases far earlier than was once possible in the nanotechnology era. Here, we review a novel approach for evaluating nanotoxicity by integrating metabolomics with metabolomic profiling and transcriptomics, which is termed "metabotranscriptomics."

The Effect of Alisma canaliculatum and Polyporus umbellatus Extracts on Adipogenic Differentiation of Human Bone Marrow Derived Mesenchymal Stromal Stem cells (택사/저령 추출물이 사람 중간엽 줄기세포의 지방세포 분화에 미치는 영향)

  • Yu, Sung-ryul;Kim, Si-hyun;Shin, Seon-mi
    • The Journal of Internal Korean Medicine
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    • v.39 no.6
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    • pp.1181-1190
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    • 2018
  • Objective: This study investigated the effect of purified medical herb extracts such as Alisma canaliculatum and Polyporus umbellatuson adipogenic differentiation of human bone marrow derived mesenchymal stromal stem cells (hBMSCs). Methods: Two different medical herb were extracted using hot distilled water. The optimal concentration of extracts were fixed at 100 ng/ml by means of cell viability and cytotoxic assay. To test the adipogenic differentiation ability of extracts, we induced the adipogenesis of hBMSCs for 21 days. At day 5, the cell was harvested to check mRNA and protein expression level of adipogenic related factors. The efficacy of lipid droplet formation was evaluated using the oil-red O staining method at days 21. Results: Two different medical herb extracts have no toxicity on hBMSCs. And two different medical herb extracts significantly decreased formation of lipid droplet compared with control groups in hBMSCs. The A. canaliculatum extract group showed the lowest mRNA and protein expression level of adipossgenic related transcription factors. This data suggests that extract of A. canaliculatum and P. umbellata decrease the adipogenic differentiation of hBMSCs. Conclusions: Our findings indicate that water-extract of A. canaliculatum and P. umbellata will be useful therapeutic reagents for prevention of obesity related disease such as diabetes, hyperlipidemia, coronary artery disease, and osteoporosis.