• Title/Summary/Keyword: cytotoxic effects

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Fine Structural Changes of the Renal Corpuscle of the Mice following the Administration of 5-Fluorouracil or Mitomycin C (5-Fluorouracil 및 Mitomycin C 투여후 생쥐 콩팥소체의 미세구조 변화)

  • Ko, Jeong-Sik;Oh, Won-Young;Kim, Jin-Gook;Park, Kyung-Ho;Ahn, E-Tay
    • Applied Microscopy
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    • v.29 no.1
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    • pp.25-41
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    • 1999
  • The experiment was performed to study the morphological responses of the renal glomeruli of the mice after administration of 5-fluorouracil or mitomycin C. 5-fluorouracil (60 mg/kg) or mitomycin-C $(400{\mu}g/kg)$ were injected subcutaneously to the animals every other day, and animals were sacrificed at 4 days or 7 days following the first injections. Pieces of tissues were observed with a JEM 100CX-II electron microscope. The observed results were as follows: 1. In the fourth day following the first injection of 5-fluorouracil or mitomycin C, components of the renal glomeruli of the mice are looked compact since they were filled with the widened the mesangium, and showed narrowing lumen of glomerular capillaries and of urinary spaces. The changes were more significant in the mitomycin C treated mice. 2. In the 5-fluorouracil treated mice, morphological changes of glomeruli were generally recovered in the seventh day, whereas the glomeruli of the mitomycin C treated mice have not shown general recovery. 3. In the fourth and seventh days following the first injection of mitomycin C, in the renal glomeruli of the mice, swollen endothelial cells, and protruded mesangeal cells into the capillary lumen are frequently observed. 4. In the fourth day following the first injection of mitomycin C, in the glomerular basal lamina of the mice, the electron densities of the lamina rara interna and the lamina rara externa were similar to the density of the lamina densa and the expanded lamina rara interna were often seen. From the above results, it is suggested that the cytotoxic effects of the mitomycin C on renal glomeruli are more severe as compared with those of 5-fluorouracil.

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Anti-oxidative and Anti-cancer Activities by Cell Cycle Regulation of Salsola collina Extract (솔장다리 추출물의 항산화 활성 및 세포주기조절에 의한 항암 활성 분석)

  • Oh, You Na;Jin, Soojung;Park, Hyun-Jin;Kwon, Hyun Ju;Kim, Byung Woo
    • Microbiology and Biotechnology Letters
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    • v.42 no.1
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    • pp.73-81
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    • 2014
  • Salsola collina, also known as Russian thistle, is widely distributed in and around waste facilities, roadsides, and drought and semi-drought areas, and is used as a traditional folk remedy in Chinese medicine for the treatment of hypertension. In this study, we have evaluated the anti-oxidative and anti-cancer activities of the ethanol extract of S. collina Pall. (EESC), and the molecular mechanisms of its anti-cancer effects on human colon carcinoma HT29 cells. EESC exhibited anti-oxidative activity through DPPH radical scavenging capacity and showed cytotoxic activity in a dose-dependent manner in HT29 cells. After EESC treatment, HT29 cells altered their morphology, becoming smaller and irregular in shape. EESC also induced cell accumulation in the G2/M phase in a dose-dependent manner, accompanied by a decrease of cell population in the G1 phase. The G2/M arrest by EESC was associated with the increased expression of cyclin-dependent kinase (CDK) inhibitor p21 and Wee1 kinase, which phosphorylates, or inactivates, Cdc2. EESC treatment induced the phosphorylation of Cdc2 and Cdc25C, and inhibited cyclin A and Cdc25C protein expression. In addition, S arrest was induced by the highest concentration of EESC treatment, associated with a decrease of cyclin A and Cdk2 expression. These findings suggest that EESC may possess remarkable anti-oxidative activity and exert an anti-cancer effect in HT29 cells by cell cycle regulation.

Intratumoral Administration of Dendritic Cells Combined with Hyperthermia Induces Both Local and Systemic Antitumor Effect in Murine Tumor Models (온열 요법 후 종양 내 주입한 수지상 세포의 국소 및 원격 항종양 효과)

  • Kwon Byung-Hyun;Kim Won-Taek;Kim Young-Kan;Kim Dong-Won
    • Radiation Oncology Journal
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    • v.24 no.1
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    • pp.51-57
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    • 2006
  • Puroose: We examined whether intratumoral (i.t.) administration of dendritic cells (DCs) into a treated tumor could induce local and systemic antitumor effects in a mouse tumor model. Methods and Materials: C57BL/6 mice were inoculated s.c. in the right and left thighs with MCA-102 fibrosarcoma cells on day 0 and on day 7, respectively. On day 7, the tumors (usually 6 mm in diameter) on the right thigh were heated by immersing the tumor-bearing leg in a circulating water bath at $43^{\circ}C$ for 30 min; thereafter, the immature DCs were i.t administered to the right thigh tumors. This immunization procedure was repeated on days 7, 14 and 21. The tumors in both the right and left thighs were measured every 7 days and the average sizes were determined by applying the following formula, tumor $size=0.5{\times}(length+width)$. Cytotoxicity assay was done to determine tumor-specific cytotoxic T-lymphocyte activity. Results: Hyperthermia induced apoptosis and heat shock proteins (HSPs) in tumor occurred maximally after 6 hr. For the local treated tumor, hyperthermia (HT) alone inhibited tumor growth compared with the untreated tumors (p<0.05), and furthermore, the i.t. administered DCs combined with hyperthermia (HT + DCs) additively inhibited tumor growth compared with HT alone (p<0.05). On the distant untreated tumor, HT alone significantly inhibited tumor growth (p<0.05), and also HT + DCs potently inhibited tumor growth (p<0.001); however, compared with HT alone, the difference was not statistically significant. In addition, HT + DCs induced strong cytotoxicity of the splenocytes against tumor cells compared to DCs or HT alone. Conclusion: HT + DCs induced apoptosis and increased the expression of HSPs, and so this induced a potent local and systemic antitumor response in tumor-bearing mice. This regimen may be beneficial for the treatment of human cancers.

Photodynamic Therapy with Photofrin Reduces Invasiveness of U87 Malignant Human Glioma Cells (교모세포종 세포주 U87에서 Photofrin을 사용한 광역학 치료가 종양 침습성에 미치는 영향)

  • Woo, Hye Kyung;Cho, Kyung-Keun;Rha, Hyung Kyun;Lee, Kyung Jin;Park, Sung Chan;Cho, Jung Ki;Park, Hea Kwan;Kang, Joon Ki;Choi, Chang Rak
    • Journal of Korean Neurosurgical Society
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    • v.30 no.sup2
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    • pp.189-196
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    • 2001
  • Objective : We tested the hypothesis that photodynamic therapy(PDT) with Photofrin inhibits tumor invasion of U87 human glioma cells using several in vitro assay to measure tumor invasiveness. The effects of PDT on cell growth, directional migration and cell invasion were investigated. Material and Method : Tumor cells were treated with Photofrin at various doses and at a fixed optical(632nm) dose of $100mJ/cm^2$. Cytotoxicity was tested using the MTT method. Invasion assays including the matrigelartificial basement membrane barrier migration and spheroid confrontation with confocal microscopic analysis were used to study the relationship between PDT and invasiveness. Result : U87 cells showed a dose dependent cytotoxic response to increasing Photofrin dose. Data from the matrigel artificial basement membrane assay indicate that PDT inhibits the U87 cell migration dose dependently. Low doses of subcytotoxic PDT treatment, such as 2.5ug/ml Photofrin dose, also appeared to significantly inhibit migration of U87 cells(p<0.05). In co-cultures between U87 cell spheroids and brain aggregates, progressive invasion with destruction of the brain aggregate occurs. The extent of tumor cell infiltration and proportion or intact brain aggregate remaining after 24h differs in Photofrin PDT treated versus Photofrin only control, with changes suggestive of a dose-response effect. Conclusion : our data indicate that PDT with Photofrin significantly inhibits the invasiveness of U87 cells, and this inhibition is dose dependent.

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Development of New Natural Antioxidants for Cosmeceuticals (천연물 유래 항산화 기능성 화장품 신소재 개발)

  • Yoo, Ick-Dong;Kim, Jong-Pyung;Kim, Won-Gon;Yun, Bong-Sik;Ryoo, In-Ja
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.31 no.4 s.54
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    • pp.349-357
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    • 2005
  • New antioxidative substances for cosmeceuticals were screened from natural resources such as microbial metabolites, mushrooms, and medicinal plants. Four antioxidants were isolated from the fungal metabolite of Eupenicillium shearii and their structures were determined to be new phenolic compounds. The compounds were designated as melanocins A, B, C, and D. Melanocins $A{\sim}D$ exhibited free radical scavenging activity on DPPH and superoxide with $EC_{50}$ values of $21{\sim}94\;and\;7{\sim}84{\mu}M$, respectively, which were stronger activity than those of ${\alpha}-tocopherol$ and BHA. Melanocin A showed anti-wrinkle effects on the UV-irrated hairless mouse skin. A novel hispidin antioxidative compound designated as inoscavin A was isolated from the fruiting body of the mushroom, Inonotus xeranticus. Inoscavin A scavenged superoxide radical with $EC_{50}$ values of $0.03{\mu}g/mL$, and inhibited rat liver microsomal lipid peroxidation with $EC_{50}$ values of $0.3{\mu}g/mL$. Benzastatins $A{\sim}G$, the novel antioxidants isolated from the culture of Streptomyces nitrosporeus showed potent lipid peroxidation inhibitory activity with $EC_{50}$ values of $3{\sim}30{\mu}M$. A cyclopentene compound with strong hypopigmentary effect was isolated from the fungal metabolite of Penicillium sp. and identifed as terrein. Terrein significantly reduced melanin levels in a melanomacyte cell line, Mel-Ab. It showed 10 times stronger activity than kojic acid, but exhibited no cytotoxic effect even in $100{\mu}M$. It was suggested that terrein reduced melanin synthesis by reducing tyrosinase production by MITF down-regulation.

Mytilin B, an Antimicrobial Peptide from the Hemocyte of the Hard-shelled Mussel, Mytilus coruscus : Isolation, Purification, and Characterization (참담치(Mytilus coruscus) 혈구(hemocyte) 유래 항균 펩타이드 mytilin B의 정제 및 특성 분석)

  • Lee, Min Jeong;Oh, Ryunkyoung;Kim, Young-Ok;Nam, Bo-Hye;Kong, Hee Jeong;Kim, Joo-Won;Park, Jung Youn;Seo, Jung-Kil;Kim, Dong-Gyun
    • Journal of Life Science
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    • v.28 no.11
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    • pp.1301-1315
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    • 2018
  • We purified an antimicrobial peptide from the acidified hemocyte extract of Mytilus coruscus by $C_{18}$ reversed-phase high-performance liquid chromatography (RP-HPLC). The peptide was 4041.866 Da based on matrix-assisted laser desorption ionization time-of-flight mass spectrophotometer (MALDI-TOF/MS) and the 25 amino acids of the N-terminus sequence were identified. Comparison of this sequence of the purified peptide with the N-terminus sequences of other antimicrobial peptides revealed 100% identity with the mytilin B precursor of Mytilus coruscus. We also identified a 312 bp open-reading frame (ORF) encoding 103 amino acids based on the obtained amino acid residues. The nucleotide sequence of this ORF and the amino acid sequence also revealed 100% identity with the mytilin B precursor of Mytilus coruscus. We synthesized two antimicrobial peptides with an alanine residue in the C-terminus, and designated them mytilin B1 and B2. These two antimicrobial peptides showed antimicrobial activity against gram-positive bacteria, including Bacillus cereus and Streptococcus parauberis (minimal effective concentration, MECs $41.6-89.7{\mu}g/ml$), gram-negative bacteria, including Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Providencia stuartii, Pseudomonas aeruginosa, and Vibrio ichthyoenteri (MECs $7.4-39.5{\mu}g/ml$), and the fungus Candida albicans (MECs $26.0-31.8{\mu}g/ml$). This antimicrobial activity was stable under heat and salt conditions. Furthermore, the peptides did not exhibit significant hemolytic activity or cytotoxic effects. These results suggest that mytilin B could be applied as alternative antibiotic agent, and they add to the understanding of the innate immunity of hard-shelled mussels.

The Study of Cosmeceutical Activities from Lentinula edodes extracts and Application a Natural Cosmetic Material (표고버섯 추출물의 화장품약리활성 검증과 천연화장품 소재로써의 활용에 관한 연구)

  • Seo, Myeong-Seong;Jang, Young-Ah;Lee, Jin-Tae
    • Journal of the Korean Applied Science and Technology
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    • v.35 no.4
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    • pp.1003-1012
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    • 2018
  • This study is for checking the possibility of Lentinula edodes as cosmetic materials. For this we carried out biological active evaluation about anti-oxidant and anti-inflammatory effects by Lentinula edodes extracts. We extracted Lentinula edodes with water and 70% ethanol and then in order to evaluate anti-oxidant activity we treated samples by concentrations (100, 500, 1000) ${\mu}g/ml$ and carried out 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, the activity of 2,2'-azino-bis ( 3-ethylbenzothiazoline-6-sulphonic acid )-diammonium salt (ABTS) cation radical scavenging and superoxide dismutase(SOD) like activity. Also, in order to evaluate effect of anti-inflammatory the samples in macrophages(RAW 264.7 cells), we carried out evaluation of cell viability, nitric oxide inhibitory activity western blot. The results of DPPH, $ABTS^+$ radical scavenging activity and SOD-like activity of the Lentinula edodes extracts increased in dose-dependent manner. The cytotoxic of samples by MTT assay showed no toxicity at the concentrations of 10, 25 and $50{\mu}g/ml$ of Lentinula edodes extract. Nitric oxide inhibition activity results showed that the extracts reduced NO productions in a concentration-dependent manner. Expression of inflammatory cytokines as $TNF-{\alpha}$, $PGE_2$ and $IL-1{\beta}$ decreased in a concentration-dependent manner and iNOS and COX-2 proteins expression rates were decreased significantly in western blot analysis. From the results of the experiment, it was comfirmed that the Lentinula edodes extracts had excellent anti-oxidant and anti-inflammatory effect and could be used as a safe natural cosmetic material in the future.

Cytotoxic Effect and Protein Expression by Korean Regional Propolis on HeLa Ovarian Cancer Cell Line (HeLa 암세포주에 대한 국산 프로폴리스의 독성 효과 및 단백질 발현 변화)

  • Kim, Sung-Kuk;Woo, Soon Ok;Han, Sang Mi;Kim, Se Gun;Bang, Kyung Won;Kim, Hyo Young;Choi, Hong Min;Moon, Hyo Jung
    • Journal of Apiculture
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    • v.34 no.3
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    • pp.245-254
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    • 2019
  • We investigated the anti-tumor effects and molecular mechanism of Brazil, China and Korean regional propolis on HeLa ovarian cancer cell line. Each propolis extracts was prepared by ethanol extraction method. Cytotoxicity of propolis extracts was determinated by EZ-cytox cell viability assay. To necessity of anti-tumor effect and molecular mechanism of propolis, we must be adjusting propolis concentration. Due to 100 ㎍/mL of propolis extract were reduced cell viability to less than 50%, we adjusted all of propolis concentration to 100 ㎍/mL. By Western blotting analysis, we confirmed that anti-tumor mechanism of Brazil, China and Korea regional propolis has significantly difference. All of propolis was activated apoptosis related molecules such as PARP, caspase-3. However, cell proliferation signaling molecules including Akt1, ERK and Bcl-2 were reduced the protein expression level. Especially, the expression of tumor suppressor protein p53 was significantly increased in propolis-treated group such as Gyeonggi, Chungbuk, Chungnam, Jeonbuk, Gyeongnam and China. The phosphorylation of Bax which as apoptosis indicator was appeared in propolis-treated group such as Gyeonggi, Gangwon, Chungnam, Gyeongbuk, China. In this results showed that the regional propolis has completely different mechanism in anti-tumor. Thus, propolis extracts may be useful source of functional materials on anti-cancer and it will be able to choose the suitable propolis for cancer therapy by analyzing individual characteristics.

Effect of Retrovirus Mediated TNF-$\alpha$ Gene Transfer to Tumor Necrosis Factor(TNF) Sensitive Tumor Cell Lines on Sensitivity to TNF (Retroviral Vector를 이용한 TNF-$\alpha$ 유전자의 이입이 암세포의 종양괴사인자(TNF) 감수성에 미치는 효과)

  • Oh, Yeon-Mok;Park, Kyeo-Yeong;Jung, Man-Pyo;Yoo, Chul-Gyu;Kim, Young-Whan;Han, Sung-Goo;Sim, Young-Soo;Han, Yong-Chol
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.2
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    • pp.87-96
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    • 1994
  • Background : Since tumor necrosis factor was discovered in 1975, TNF has been well known about its cytotoxic effect on tumor cells in vivo and in vitro. According to the recent improvement of molecular biological techinques, it is possible that exogenous TNF gene is transferred to tumor cells and is expressed in theirs. By virtue of TNF gene transfer, we have expected that TNF expressed in TNF-gene-transferred tumor cells would kill tumor cells in vivo without systemic side effect. The expected mechanisms in which antitumor effects of TNF expressed in TNF-gene-transferred tumor cells are working would be as followings. In the first mechanism, TNF expressed in TNF-gene-transferred tumor cells would kill tumor cells around(like homicide). In the second mechanism, TNF expressed in TNF-gene-transferred tumor cells would kill themselves(like suicide). In the third mechanism, TNF expressed in TNF-gene-transferred tumor cells would recruit immune effector cells and kill tumor cells indirectly. In the last mechanism, TNF expressed in TNF-gene-transferred tumor cells would augment cytokine such as interferon-$\gamma$ to kill tumor cells. Among these four mechanisms of antitumor effect, only the second mechanism has not been established yet. Therefore, to elucidate the second mechanism, We performed this study. Method : We transferred TNF-$\alpha$ gene to NCI-H2058, a human mesothelioma cell line and WEHI164, a murine fibrosarcoma cell line by using retroviral vector(pLT12SNTNF). And, We determined by using MTT assay whether TNF expressed in TNF-gene-transferred tumor cell lines would kill themselves like suicide or not. Then, if TNF-gene-transferred tumor cell lines would not suicide themselves, I would know more about the TNF sensitivity of TNF-gene-transferred tumor cell lines to exogenous TNF also by MTT assay. Result : NCI-H2058 and WEHI164 which were sensitive to TNF, became far less sensitive to endogenous and exogenous TNF after being transferred TNF-$\alpha$ gene to. Conclusion : TNF-gene-transfer to NCI-H2058 and WEHI164 gave them resistance to TNF.

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