• Title/Summary/Keyword: cytotoxicities

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CSE1L/CAS, a microtubule-associated protein, inhibits taxol (paclitaxel)-induced apoptosis but enhances cancer cell apoptosis induced by various chemotherapeutic drugs

  • Liao, Ching-Fong;Luo, Shue-Fen;Shen, Tzu-Yun;Lin, Chin-Huang;Chien, Jung-Tsun;Du, Shin-Yi;Jiang, Ming-Chung
    • BMB Reports
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    • v.41 no.3
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    • pp.210-216
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    • 2008
  • CSE1L/CAS, a microtubule-associated, cellular apoptosis susceptibility protein, is highly expressed in various cancers. Microtubules are the target of paclitaxel-induced apoptosis. We studied the effects of increased or reduced CAS expression on cancer cell apoptosis induced by chemotherapeutic drugs including paclitaxel. Our results showed that CAS overexpression enhanced apoptosis induced by doxorubicin, 5-fluorour-acil, cisplatin, and tamoxifen, but inhibited paclitaxel-induced apoptosis of cancer cells. Reductions in CAS produced opposite results. CAS overexpression enhanced p53 accumulation induced by doxorubicin, 5-fluorouracil, cisplatin, tamoxifen, and etoposide. CAS was associated with $\alpha$-tubulin and $\beta$-tubulin and enhanced the association between $\alpha$-tubulin and $\beta$-tubulin. Paclitaxel can induce G2/M phase cell cycle arrest and microtubule aster formation during apoptosis induction, but CAS overexpression reduced paclitaxel-induced G2/M phase cell cycle arrest and microtubule aster formation. Our results indicate that CAS may play an important role in regulating the cytotoxicities of chemotherapeutic drugs used in cancer chemotherapy against cancer cells.

EBV-Based Plasmid Encoding HSV-TK for Cytocidal Gene Therapy (HSV-TK 유전자를 암호화하는 EBV 유래 플라스미드를 이용한 유전자 치료)

  • Oh, Sang-Taek;Min, Kyoung-Ah;Kim, Chong-Kook;Lee, Suk-Kyeong
    • Journal of Pharmaceutical Investigation
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    • v.33 no.4
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    • pp.267-272
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    • 2003
  • Herpes simplex virus (HSV) thymidine kinase (TK) has been widely used for suicidal gene therapy in combination with nucleoside analogs such as ganciclovir (GCV). The use of HSV-TK is limited due to the side effect of GCV at high concentrations. Previous studies showed that stable transfectants of mutant HSV-TK with enhanced affinity to GCV were killed at lower GCV concentrations. In this study, we tested whether mutant HSV-TK can provide enhanced suicidal effect when transiently transfected with Epstein-Barr virus (EBV)-based plasmid. EBV-based plasmid which contains OriP and EBNA-1 sequence is well known for a stable episomal maintenance in human cells. Optimal transfection condition was assessed for SNU-638 gastric cancer cell line using polyetylnimine (PEI). Maximum transfection efficiency was achieved when DNA:PEI was 1:3 (w/v). Cytotoxicities of mutant and wild type HSV-TK were compared before and after partially selecting transfected cells. The cells were sensitive to $100\;{\mu}g/ml$ hygromycin. Following GCV treatment, more cells were killed after hygromycin selection than before selection. The mutant HSV-TK showed enhanced cytotoxicity compared with the wild type HSV-TK. Our results suggest that the EBV-based plasmid encoding mutant HSV-TK may be useful to treat the diseases caused by uncontrolled cell proliferation such as cancer and rheumatoid arthritis.

Physical and Chemical Composition, Anti-Microbial Activity and Cytotoxicity of Kiwifruit Skin (식품표시 관련 교육경험에 따른 중학생들의 식품표시에 대한 인식과 활용실태)

  • Heo, Buk-Gu;Park, Yong-Seo;Im, Myung-Hee;Oh, Kyung-Taek;Cho, Ja-Yong
    • The Korean Journal of Community Living Science
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    • v.20 no.1
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    • pp.61-69
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    • 2009
  • This study was conducted to examine the chemical composition of kiwifruit skin, and to est its anti-microbial activities and cytotoxicities, thus, exploring ways for the economic utilization of kiwifruit skin. Four varieties of kiwifruit were examined: Daeheung, Bidan, Haegeum No.1 and Hayward. Vitamin C content in the fruit skins of Bidan, Daeheung, Haegeum No.1 and Hayward were 72.44, 67.22, 62.51 and 61.44mg/100g, respectively. Total amino acids content in the fruit skins of Bidan, Haegeum No.1, Hayward and Daeheung ere 808.31, 706.02, 629.07 and 464.83mg/100g dry weight, respectively. K and Ca content ere $17.20-45.70{\mu}g/mL$ and $4.58-10.15{\mu}g/mL$. While, other inorganic matter contents were below $4.89{\mu}g/mL$. Anti-microbial activity of kiwifruit skin extracts, in terms of the diameter of inhibition zone when tested against five gram positive and three gram negative microbial trains (even in the concentration of 2,000mg/L), was less than 14.1mm. The hyperplasia inhibition of lung cancer cells by methanol extracts from Bidan and Haegeum No.1 using concentrations of 800mg/L were 27.7% and 14.5%, however, those from Daeheung and Hayward were below 3% Consequently, it will be useful to know that kiwifruit skin can be added to processed goods which demand for higher concentrations of vitamin C, amino acids, K and Ca.

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Effect of Mahwangyunpye-tang on Secretion of Airway Mucin and Tracheal Smooth Muscle (마황윤폐탕(麻黃潤肺湯)이 호흡기 뮤신 분비 및 기관지 평활근에 미치는 영향)

  • Hwang, Ji-Ho;Yang, Su-Young;Byun, Jun-Seop;Park, Yang-Chun
    • The Journal of Internal Korean Medicine
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    • v.28 no.4
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    • pp.797-807
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    • 2007
  • Objectives : The purpose of this study was to investigate whether Mahwangyunpye-tang(MYT) significantly affects mucin secretion from airway epithelial cells. Methods : Confluent hamster tracheal surface epithelial (HTSE) cells were metabolically radiolabeled with 3H-glucosamine for 24 hrs and chased for 30 min in the presence of MYT to assess the effect of the agent on 3H-mucin secretion. Total elution profiles of control spent media and treatment sample through Sepharose CL-4B column were analyzed. Effect of MYT on contractility of isolated tracheal smooth muscle was investigated; also investigated was effect of the agent on MUC5AC gene expression in cultured NCI-H292 cells. Possible cytotoxicities of the agent were assessed both by measuring lactate dehydrogenase (LDH) release from HTSE cells and examining the rate of survival and proliferation of NCI-H292 cells. Results : MYT significantly increased mucin secretion from cultured HTSE cells, without significant cytotoxicity. MYT chiefly affected the 'mucin' secretion. MYT inhibited Acetylcholine-induced contraction of isolated tracheal smooth muscle. MYT did not significantly affect the expression levels of MUC 5AC gene in cultured NCI-H292 cells. Conclusions : Based on the above results, it is suggested that MYT increased mucin secretion from cultured HTSE cells without significant cytotoxicity and inhibited contraction of isolated tracheal smooth muscle.

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Cytotoxicity of Shikonin Metabolites with Biotransformation of Human Intestinal Bacteria

  • Min, Byung-Sun;Meselhy, Meselhy-R.;Hattori, Masao;Kim, Hwan-Mook;Kim, Young-Ho
    • Journal of Microbiology and Biotechnology
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    • v.10 no.4
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    • pp.514-517
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    • 2000
  • Abstracts Six shikonin metabolites were obtained from human intestinal bacteria, Bacteriodes fragilis subsp. thetaotus. following biotransformation. The transformation of shikonin (1) was performed anaerobically for 3 day at $37^{\circ}C$ in thc bacterial suspension of B. Fagilis which was cultured overnight in GAM broth. The incubation mixture \vas extracted with EtGAc Lo give a dark-brown residue. The residue was apphed to a silica gel column, which was eluted successively with hexane (Fr. A), $CHCl_3$ (Fr. B), and $CHCl_3$:MeOH (9:I) (Fr. C). Six metabolites. Fr.A (2 and 3), Fr. B (6 and 7), and Fr. C (4 and 5) were isolated by repeated silica gel column chromatography, preparatlVe TLC, followed by Sephadex LH-20. In vitro cytotoxicities were tested against human tumor cell lines; PC-3 (prostate), ACHN (renal), A549 (lung), SW620 (colon), KS62 (leukemia), and Du145 (prostate). The shikonin metabolites 2. 4, 5, and 6 showed weaker cytotoxicity than the parenL shikonin (1). whereas shikonin monomenc metabolite 3 ($ED_{50}{\;}O.44-{\;}1.22{\;}\mu\textrm{g}/ml$) and dimeric metabolite 7 ($ED_{50}{\;}O.48-{\;}2.35{\;}\mu\textrm{g}/ml$) exhibited stronger activities compared with adriamycin, which was used as the positive control.ontrol.

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Increased Refolding Yield of Disulfide Bond Bridged Fab-Toxin Homodimers by the Insertion of CH3 Domains

  • Song Jeong-Wha;Won Jae-Seon;Lee Yong-Chan;Choe Mu-Hyeon
    • Journal of Microbiology and Biotechnology
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    • v.16 no.7
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    • pp.1104-1110
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    • 2006
  • Recombinant antibody-toxin is a bifunctional protein that binds and kills a target cell expressing a specific antigen on the surface of the cell, and its structure is chimeric, in which a toxin is fused to an antigen-binding domain such as scFv or Fab. Divalent antibody-toxin molecules showed higher cytotoxicities against cancer cell lines than monovalent molecules. However, the yields of the divalent molecules were very low. In this study, we introduced the CH2, CH3, or CH2-CH3 (=Fc) domain of antibody in the middle of the Fab-toxin between the hinge region of human IgG1 and the toxin domain to increase the yield. The covalently bonded dimer could be formed by three disulfide bridges from cysteine residues in the hinge region. The molecule with the CH3 domain showed about 3-fold higher dimerization yield than previously constructed Fab-toxin molecules, while maintaining the cytotoxic activity comparable to that of scFv-toxin. However, the introduction of CH2 or Fc domain to the same position showed little effect on the dimerization yield. We also observed that the introduction of the CH3 region made it possible to form noncovalently associated dimer molecules.

The Effects of 5-benzylacyclouridine on the Cytotoxicities of Fluorinated Pyrimidine Antimetabolic Agents in L5178Y Cells (L5187Y 세포에 대한 불화피리미딘 대사억제제 독성에 관한 Benzylacyclouridine의 영향)

  • Lee, Kang-Hyun;Cha, Sung-Man
    • The Korean Journal of Pharmacology
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    • v.26 no.1
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    • pp.91-100
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    • 1990
  • The benzylacycoluridines (BAU and BBAU) are potent and specific inhibitors of uridine phosphorylase (UrdPase). In contrast to the report that benzylacyclouridines potentiated 5-fluoro-2'-deoxyuridine (FdUrd) cytotoxicity against human solid tumor cells (Cancer Res., 44:1852, 1984), continuous exposure of mouse lymphoma L5178Y cells, to FdURd, 5-fluorouridine (FUrd), 5'-deoxy-5-fluorouridine (5'-dFUrd), or 5-fluorouracil (FUra) showed no potentiation of cytotoxicity by benzylacyclouridines. In fact, under the conditions employed, benzylacycoluridines protected the cells from the cytotoxicity of FdUrd, FUrd, or 5'-dFUrd, but not FUra in a dose dependent manner. Intraperitoneal coadministration of BAU or BBAU and a 5-fluorinated pyrimidine (i.e., FdUrd, FUrd, or FUra), to mice bearing L5178Y cells also did not significantly increase the life span compared to those treated with the antimetabolites alone. Anabolism of these nucleosides through the sequential action of UrdPase and orotate phosphoribosyltransferase (OPRTase), inhibition of nucleoside transport by benzylacyclouridines, or both could be responsible for the ineffectiveness of UrdPase inhibitors to potentiate the antineoplastic activity of fluoropvrimidines in L5178Y cells.

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Effects of Seonbangpaedok-tang and Sigyeongcheongpye-tang on PMA-induced Production of Airway Mucin and Expression of MUC5AC (선방패독탕(仙方敗毒湯)과 시경청폐탕(柴梗淸肺湯)이 NCI-H292 세포에서 PMA로 유발된 기도뮤신의 생성과 MUC5AC 발현에 미치는 영향)

  • Nam, Tae-Heung;Park, Yang-Chun
    • The Journal of Korean Medicine
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    • v.29 no.4
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    • pp.123-132
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    • 2008
  • Objective: In this study, the author tried to investigate whether revised Seonbangpaedok-tang (SPT) and Sigyeongcheongpye-tang (SCT) significantly effects both PMA-induced mucin production and MUC5AC gene expression from airway epithelial cells. Objective: In this study, the author tried to investigate whether revised Seonbangpaedok-tang (SPT) and Sigyeongcheongpye-tang (SCT) significantly affects both PMA-induced mucin production and MUC5AC gene expression from airway epithelial cells. Materials and Methods: Confluent NCI-H292 cells were pretreated for 30 min in the presence of SPT and SCT and treated with PMA (10 ng/$m{\ell}$), to assess the effects of the agents on PMA-induced mucin production by enzyme-linked immunosorbent assay (ELISA). Also, the effects of the agents on PMA-induced MUC5AC gene expression from the same cells were investigated. Possible cytotoxicities of the agent were assessed by measuring the rate of survival and proliferation of NCI-H292 cells after treatment of agents during 48 hrs. Results: (1) SPT and SCT did not show significant cytotoxicity to NCI-H292 cells; (2) SPT significantly inhibitedthe expression levels of PMA-induced MUC5AC gene in NCI-H292 cells. SCT slightly decreased the expression levels of PMA-induced MUC5AC gene; (3) SPT significantly decreased PMA-induced mucin production from NCI-H292 cells. However, SCT did not affect mucin production. Conclusion: Theseresults suggest that SPT can not only affect the production of mucin but also the expression of the mucin gene and this explains the traditional use of SPT in oriental medicine. The effects of SPT and SCT with their components should be further investigated using animal experimental models that reflect pathophysiology of airway diseases via ongoing studies.

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Nypa fruticans wurmb regulates the secretion level of inflammatory cytokines in vitro models.

  • Jin, Yu-Mi;Kim, Seong-Seon;Lee, Jong-Hyun;Jeon, Yong-Deok;Jin, Jong-Sik
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2018.10a
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    • pp.128-128
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    • 2018
  • Nypa fruticans wurmb (NF) has been used as traditional medicinal food in Asian countries. Especially, NF has been used for conventional medicine to treat inflammatory periodontal diseases. Previous studies have been shown that NF has large amount of useful constituents such as phenolic acids, polyphenols and flavonoids. Also, NF is known as having medicinal effects such as anti-oxidant, anti-inflammatory and cholesterol-lowering effects. NF has recently been attracted to use complementary medicinal food on inflammatory diseases in Korea. However, there are no obvious effects in inflammatory and metabolic diseases also mechanisms has been studied yet. The purpose of this study was to investigate the anti-inflammatory effects of NF and steamed-NF (SNF), which recently has been used as health food, using Human keratinocyte cell line (HaCaT) and Human mast cell line (HMC-1). The cytotoxicities of NF and SNF were measured by using MTT assays in HaCaT cells and HMC-1 cell. To evaluate anti-inflammatory effects of NF and SNF, HaCaT cells were stimulated with tumor necrosis factor $(TNF)-{\alpha}$ and Interferon $(IFN)-{\gamma}$. Also, HMC-1 cells were stimulated with phorbol-12-myristate-13-acetate (PMA) and A23187 calcium ionophore (A23187) to induce allergic inflammation. Inflammatory cytokine were measured by enzyme-linked immunosorbent assay (ELISA). In this result, the extract of NF and SNF (0.01 - 1mg/ml) did not show cytotoxicity in HaCaT cells and HMC-1 cells. In addition, the NF and SNF suppressed the production of interleukin (IL)-6 and IL-8 in HaCaT cells at highest concentration. Furthermore, the treatment of SNF significantly inhibited the secretion level of IL-8 in PMA plus A23187-stimulated HMC-1 cells compared with NF treatment group. These results suggest that the extract of NF and SNF may serve as a potential therapy for skin inflammatory diseases.

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Cytotoxicity of Methanol Extracts from Cudrania tricuspidata Bureau (꾸지뽕나무 메탄올 추출물의 세포독성)

  • Choi, So-Ra;You, Dong-Hyun;Jang, Ik;Ahn, Min-Sil;Song, Eun-Ju;Seo, Sang-Young;Choi, Min-Kyung;Kim, Young-Sun;Kim, Myung-Kon;Choi, Dong-Geun
    • Korean Journal of Medicinal Crop Science
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    • v.20 no.3
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    • pp.153-158
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    • 2012
  • In order to develop as a natural source of anticancer materials of Cudrania tricuspidata, the cytotoxicity of methanol extracts by harvesting parts and times against 8 cell lines including 293 (normal kidney cells) and A-431 (epidermoid carcinoma cells) were investigated using MTT assay. All harvesting parts had hardly cytotoxicity against 293. And methanol extracts of stem bark and root bark showed very high cytotoxicities against 7 cancer cell lines. The cytotoxicity was the highest against HeLa (cervix adenocarcinoma cells) and followed by MCF-7 (breast adenocarcinoma cells), AGS (stomach adenocarcinoma cells), HT-29 (colon adenocarcinoma cells), HepG2 (hepatoblastoma cells), A549 (lung carcinoma cells) and A-431. By the way, leaf extract had a cytotoxicity against only AGS and ripe fruit extract had no cytotoxicity. Among harvesting times, the cytotoxicity of root bark were high from April to September but that of stem bark showed a little difference. These results showed that anticancer activities of Cudrania tricuspidata extracts were eventful changes by harvesting parts and times.