• Title/Summary/Keyword: Antitumor

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The Anticancer Effects and Drug Metabolic Enzyme Change by Oral Intake of Agrimonia Pilosa Ledeb (선학초(짚신나물) 경구투여시 항암효과 탐색 및 약물 대사효소의 변화)

  • Rhee, Si-Hyung;Jung, Hee;Lee, Ju-Ah;Go, Ho-Yeon;Choi, Yu-Kyung;Park, Jong-Hyung;Kim, Ji-Hye;Ko, Seong-Kyu;Jun, Chan-Yong
    • Journal of Society of Preventive Korean Medicine
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    • v.13 no.2
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    • pp.51-64
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    • 2009
  • Objective : This research was aimed to investigate the anti-tumor effect, safety, mechanism and metabolizing enzyme of Agrimonia pilosa LEDEB(APL) in female C57B/L mouse. Methods : At first, to evaluate the anti-tumor activity of APL, we divided into four groups, normal, control, APL100(100mg/kg), APL150(150mg/kg). LLC obtained American Type Culture Collection was used. LLC had been inoculated to induce tumor. To measure the anti-tumor effect of APL, we calibrate tumor size and weight. To study for mechanism of anti-tumor in APL, we used western blotting and to know metabolizing enzyme in APL we used to real-time PCR. Results : APL100, APL150 inhibited tumor growth after medicine injected. APL did not only induced caspase-dependent apoptosis in LLC-bearing mouse tumor. In APL100, it were decreased 72% in CYP3A11. In APL150, it were decreased 62%, 75% in CYP3A11 and MRP1a respectively. Conclusion : These results suggests that APL has some anti-tumor effects in female C57B/L mouse tumor. APL should be careful use with other drugs related with CYP3A11 or MRP1a.

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Induction of Dectin-1 Expression and Intracellular Signal Transduction by β-Glucan of Ganoderma lucidum (불로초의 β-Glucan에 의한 Dectin-1 발현 유도와 세포 내 신호전달)

  • Ryu, Han Wook;Kim, Ha Won
    • The Korean Journal of Mycology
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    • v.46 no.2
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    • pp.161-176
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    • 2018
  • Fungal ${\beta}$-glucan, known to have immunostimulatory and antitumor activities, can be recognized by host immune cells as one of the pathogen-associated molecular patterns (PAMPs). Although there are several reports on the diverse immunostimulatory activities of ${\beta}$-glucan, little is known about the intracellular signal transduction of ${\beta}$-glucan. Stimulation of RAW264.7 macrophage cells with ${\beta}$-glucan from Ganoderma lucidum induced the expressions of dectin-1, toll-like receptor 2 (TLR2), TLR4, and TLR6 at the transcription stage. Treatment with ${\beta}$-glucan also induced inflammatory mediators such as macrophage inflammatory proteins (MIP)-$1{\alpha}$, MIP-$1{\beta}$, MIP-$1{\gamma}$, interleukin (IL)-$1{\beta}$, and tumor necrosis factor (TNF)-${\alpha}$. Treatment of the cells with polymyxin B, an inhibitor of lipopolysaccharides (LPS), blocked the induction of inflammatory mediators in LPS- or ${\beta}$-glucan-stimulated systems. Pretreatment of the cells in our cell culture system with LY294002, a phosphoinositide 3-kinase (PI3K) inhibitor, or U0126, a mitogen-activated protein kinase/extracellular-signal-regulated kinase (MAPK/ERK) kinase (MEK)1/MEK2 inhibitor, led to a reduction in the induction of inflammatory mediators in a concentration-dependent manner. These results show that stimulation of the macrophage cells by ${\beta}$-glucan induced the expressions of both dectin-1 and TLRs. We also found that the PI3K/Akt and MEK pathways were involved in the induction of inflammatory mediators in macrophage cells during intracellular signal transduction of ${\beta}$-glucan.

Characteristics of BCNU-loaded PLGA Wafers (BCNU를 함유한 생분해성 PLGA 웨이퍼의 특성분석)

  • 안태군;강희정;이진수;성하수;정제교
    • Polymer(Korea)
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    • v.26 no.5
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    • pp.691-700
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    • 2002
  • Interstitial therapy using biodegradable polymeric device loaded with anticancer agent can deliver the drug to the tumor site at high concentration, resulting in an increase of therapeutic efficacy. 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU, carmustine) is most commonly used as chemotherapeutic agent for brain tumors. The design of implantable device is regarded as an important factor lot the efficient delivery of antitumor agent to targeting site. In order to control the release profile of drug, the release pattern of BCNU with the changes of various dimension and additives was investigated. The PLGA wafers containing 3.85, 10, 20 and 30% of BCNU were prepared in various shape (diameter of 3, 5 and 10 mm, thickness of 0.5, 1 and 2 mm) by direct compression method. In vitro drug release profile of BCNU-loaded PLGA wafers could be controlled by changing the dimension of wafers such as initial drug content, weight, diameter, thickness, volume and surface area of wafers, as well as PLGA molecular weight and additives. Drug release from BCNU-loaded PLGA wafers was facilitated with an increase of BCNU-loading amount or presence of poly(N-vinylpyrrolidone)(PVP) or sodium chloride (NaCl). The effects of various geometric factors and additives on the BCNU release pattern were confirmed by the investigation of mass loss and morphology of BCNU-loaded PLGA wafers.

Influence of Hwanhonsan Extract against Chemically Induced and Xenografted Mice Tumor (환혼산(還魂散)이 실험적(實驗的)으로 유발(誘發)한 종양(腫瘍)에 미치는 영향(影響))

  • Song, Hyo-Won;Ryu, Do-Gon;Cho, Dong-Ki;Um, Sang-Sub;Kang, Sung-Do;Go, Jeoin-Soo;Sung, Yeun-Kyung;Yun, Young-Gap;Cho, Nam-Su;Lee, Chun-Woo;Kang, Soon-Soo
    • Journal of Oriental Physiology
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    • v.14 no.2 s.20
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    • pp.229-237
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    • 1999
  • Hwanhonsan has been used for curing tumor as a Oriental medicine without any experimental evidence to support the rational basis for their clinical use. This experiment was carried out to evaluate the possible therapeutic or antitumoral effects of Hwanhonsan extract against cancer, and to study some mechanisms responsible for its effect. Some kind of tumors were induced by the typical application of 3-methylcholanthrene(MCA) or by the implantation of malignant tumor cells such as leukemia cells(3LL cells) or sarcoma cells(S180 cells) and FasII cells. Treatment of the Hwanhonsan extract(daily 1 mg/mouse, i.p.) was continued for 7 days prior to tumor induction and after that the treatment was lasted for 20 hrs. Against squamous cell carcinoma induced by MCA, Hwanhonsan decreased. not only the frequency of tumor production but also the number and weight of tumors per tumor bearing mice(TBM). Hwanhonsan also significantly suppressed the development of 3LL cells and S180 cells implanted tumors by frequency and their size, and some developed tumors were regressed by the continuous treatment of Hwanhonsan extract into TBM. However, when tumor was induced by FsaII cells implantation, the growth of implanted cells in mice was delayed by the water extract of Hwanhonsan until 7 days and then rapid growth ensued. In vitro treatment of Hwanhonsan extract had no inhibitory effect on the tumor induced by some kind of cell lines such as A431 cells strain but it significantly inhibited the proliferation of 3LL cells, S180 cells. These results suggested that Hwanhonsan extract exhibited a significant prophylactic benefits against tumors and its antitumor activity was manifested depending on the type of tumor cells.

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Studies on the Antitumor Activity of Gamisoam-san via Suppressing Angiogenesis and Growth Factor Expression (혈관신생 및 이식암세포증식 억제를 통한 가미소암산의 항암작용연구)

  • Yoon Sung Chan;Ahn Seong Hun;Mun Yean Ja;Kim Jin Kyeong;Choo Young Kug;Jung Kyu Yong;Kim Yeong Mok;Woo Won Hong
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.4
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    • pp.969-979
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    • 2003
  • Gamisoamsan is a prescription originated in Soamsan which is known as an anti-cancer remedy in the traditional Korean Medicine. To enhance the synergic effects of anti-cancer activity of Soamsan, this study reconstituted the original components of Soamsan with a slight modification and produced a novel herbal remedy, namely Gamisoamsan. To investigate the effects of Gamisoamsan on anti-cancer reaction, I studied the effects of Gamisoamsan on angiogenesis via chorioallantoic membrane (CAM) assay, corneal neovascularization assay and the effects on expression of growth factor which are VEGF, TGF-β, bFGF and IMUP-1. Anti-cancer effects of Gamisoamsan was also abserved through hematological parameters, tumor volume and survival rate in mice. Gamisoamsan inhibited embryonic angiogenesis of blood vessels in CAM assay and inhibited neovascularization of ral cornea. Gamisoamsan reduced cell proliferation in HT1080 cells and IC50 was 2.18 ㎎/㎖ Gamisoamsan reduced the expression of VEGF, TGF-β, bFGF and IMUP-1 which was known as vascular growth factor and this effects of Gamisoamsan was predominant than VP-16. The treatment of Gamisoamsan decreased the CT-26 cell inoculated-tumor volume in mice colon adenocarcinoma and increased mice survival which was inoculated CT-26 cells. The results of the present study suggest that Gamisoamsan extracts has a potential anti-tumor activity and may be an useful remedy to prevent and/or treat cancer.

Helixor A Inhibits Angiogenesis in vitro Via Upregutation of Thrombospondin-1 (Helixor A는 시험관 내에서 thrombospondin-1의 상승조절을 통해 신혈관생성을 억제한다.)

  • Yeom Dong-Hoon;Hong Kyong-Ja
    • Journal of Life Science
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    • v.15 no.6 s.73
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    • pp.895-903
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    • 2005
  • Thrombospondin-1 (TSP-1), a negative regulator in tumor growth and angiogenesis, is cell-type specifically regulated under pathological conditions or by extracellular stimuli, and the regulation of TSP-1 gene expression is important for developing new approaches in tumor therapy. Mistletoe is a parasitir plant that have been used for immunomodulation and antitumor therapy. Helixor A is an aqueous part of mistletoes extract. Here we showed that TSP-1 expression was significantly induced at both mRNA and protein levels in the Hepatocarcinorna cell line (Hep3B) and primary bovine endothelial cell line (BAE) exposed to Helixor A. Our promoter analysis confirmed that the expression of TSP-1 gene was regulated by Helixor A at the transcriptional level. In cell invasion assay, the conditioned media obtained from treatment of these cells significantly reduced the number of invasive cells and also inhibited capillary-like tube formation of BAE cells on Matrigel. Moreover, the inhibitory efforts of the conditioned media on cell invasion and tube formation were reversed by blocking with anti-TSP-1 neutralizing antibodies, suggesting that TSP-1 is involved in Helixor A-indured antiangiogenic effect. Taken together, our results suggest that Helixor A have an antiangiogenic effects through upregulation of TSP-1.

Effects of Cyclophosphamide on Immunological Memory in Mice (Cyclophosphamide가 마우스의 면역기억에 미치는 영향)

  • Park, Young-Min;Park, Yoon-Kyu;Ahn, Woo-Sup;Ha, Tai-You
    • The Journal of the Korean Society for Microbiology
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    • v.22 no.2
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    • pp.175-184
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    • 1987
  • The use of alkylating agent cyclophosphamide(CY), a widely used antitumor drug is well known as a potent immunosuppressant and has been used as a probe for investigating the functional capabilities of lymphocyte subsets of both T and B cells that play an important role in the regulation of the immune response. The present study was undertaken in an effort to assess the effects of CY on immunological memory in murine model. CY, given as a single dose of CY(250mg/kg) before sensitization with sheep red blood cells(SRBC) enhanced the primary response of Arthus and delayed-type hypersensitivity(DTH), as measured by footpad swelling reaction, but suppressed their tertiary DTH response. The similar CY pretreatment enhanced both the primary and tertiary hemagglutinin(HA) responses to SRBC, and the tertiary antibody response against polyvinylpyrroridone(PVP), a thymus-independent antigen but not the primary response against PVP. CY, given as a single dose of 250mg/kg 2 days before the primary immunization and two doses of 100mg/kg 2 days before the secondary and tertiary immunization, markedly suppressed the tertiary DTH and HA responses to SRBC. However, CY, given as small multiple daily doses(10mg/kg) over 4 days before sensitization but not after sensitization, enhanced the secondary HA response to SRBC. Contact sensitivity to dinitrofluorobenzene(DNFB) was suppressed by the drug, given either as a single large dose(300mg/kg) or as multiple dose(10mg/kg) administered 2 days before, together with or after DNFB sensitization. This suppression was more pronounced and more significant when CY was given as multiple dose. However, the enhancement of the secondary contact sensitivity to DNFB by CY was not clear-cut. The splenectomy appears to increase the enhancing effect of CY on contact sensitivity. These results suggest that CY selectively influences the immune response depending on the time of the drug administration relative to immunization and that the secondary or tertiary immune response involve memory cells with different susceptibilities to CY. Moreover, these results suggest that multiple low doses may sesectivley inhibit suppressor T cell proliferation involving DTH, HA or contact sensitivity without effecting helper T cells, but high doses presumably inhibit helper T cells and suppressor T cells with effecting B cells.

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Effect of sun ginseng potentiation on epirubicin and paclitaxel-induced apoptosis in human cervical cancer cells

  • Lin, Yingjia;Jiang, Dan;Li, Yang;Han, Xinye;Yu, Di;Park, Jeong Hill;Jin, Ying-Hua
    • Journal of Ginseng Research
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    • v.39 no.1
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    • pp.22-28
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    • 2015
  • Background: Sun ginseng (SG), a specific formulation of quality-controlled red ginseng, contains approximately equal amounts of three major ginsenosides (RK1, Rg3, and Rg5), which reportedly has antitumor-promoting activities in animal models. Methods: MTT assay was used to assess whether SG can potentiate the anticancer activity of epirubicin or paclitaxel in human cervical adenocarcinoma HeLa cells, human colon cancer SW111C cells, and SW480 cells; apoptosis status was analyzed by annexin V-FITC and PI and analyzed by flow cytometry; and apoptosis pathway was studied by analysis of caspase-3, -8, and -9 activation, mitochondrial accumulation of Bax and Bak, and cytochrome c release. Results: SG remarkably enhances cancer cell death induced by epirubicin or paclitaxel in human cervical adenocarcinoma HeLa cells, human colon cancer SW111C cells, and SW480 cells. Results of the mechanism study highlighted the cooperation between SG and epirubicin or paclitaxel in activating caspase-3 and -9 but not caspase-8. Moreover, SG significantly increased the mitochondrial accumulation of both Bax and Bak triggered by epirubicin or paclitaxel as well as the subsequent release of cytochrome c in the targeted cells. Conclusion: SG significantly potentiated the anticancer activities of epirubicin and paclitaxel in a synergistic manner. These effects were associated with the increased mitochondrial accumulation of both Bax and Bak that led to an enhanced cytochrome c release, caspase-9/-3 activation, and apoptosis. Treating cancer cells by combining epirubicin and paclitaxel with SG may prove to be a novel strategy for enhancing the efficacy of the two drug types.

Effect Naetakchungumsankamibang on Skin tumor induced by 3-MCA and Immunological Response (內托千金散加味方이 3-MCA로 誘發된 皮膚癌 및 免疫調節作用에 미치는 影響)

  • Kim, Hee-taek;Roh, Seok-seon
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.12 no.2
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    • pp.20-52
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    • 1999
  • In order to investigate the effect of Naetakchungumsankamibang(NTCGS) water extract on the skin tumor induced by 3-MCA and immunological responses in mice, the cytotoxicity against SK-MEL-2 cells and total number of tumors induced by 3-MCA were measured. The numbers of WBC, platelets and RBC, plaque forming cells, hemagglutinin titer, hemolysis titer, carbon clearance, proliferation of splenocyte by thymidine uptake assay, splenic leukocyte by FACS analysis and $TNF-{\alpha}$ were also measured for the evaluation of the immunological responses. The results were obtained as follows: 1. In cytotoxicity against SK-MEL-2 cells, concentration inhibiting cell growth up to below $20\%$ of control was recognized at 1mg/ml of NTCGS. 2. In Inhibitory effect on the skin tumor induced by 3-MCA, the results showed a strong inhibitory effect of NTCGS. 3. In hematological changes in the tumor bearing mice, the numbers of WBC decreased significantly in NTCGS treated group as compared with control. 4. In hematological changes in the tumor bearing mice, the numbers of platelets increased significantly in NTCGS treated group as compared with control. 5. In hematological changes in the tumor bearing mice, the numbers of RBC increased with no significance in NTCGS treated group as compared with control. 6. Effects of the plaque forming cells in the tumor bearing mice, NTCGS treated group exhibited a significant effect compared with control. 7. In terms of the effects on hemagglutinin titer, NTCGS treated group showed higher level than control, without significance. 8. In terms of the effects on hemolysis titer, NTCGS treated group showed higher level than control, without significance. 9. In terms of the effects on phagocytic index K in Balb/C mice, NTCGS treated group showed significant difference from control. 10. In terms of the effects on proliferation of splenocyte by thymidine uptake assay, NTCGS showed significant effect at the concentration of 0.5mg/ml. 11. In terms of the effects on splenic leukocyte of Balb/C mice by FACS analysis, NTCGS treated group showed significantly higher level of helper T cell, B cell and macrophage than in control. 12. In terms of the effects on the secretion of $TNF-{\alpha}$, the treated group showed significant effect at the concentration of 1mg/ml of NTCGS. Based on the results summarized above, NTCGS is considered to have antitumor activity and immunological responses against skin tumor, and to be usable fur the treatment.

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Biological activities and physicochemical properties of polysaccharides from Gloiopeltis furcata prepared by using various enzymes (효소종류에 따른 불등풀가사리 유래 다당류의 이화학적 특성 및 생리활성)

  • Lee, Dae-Hoon;Hong, Joo-Heon
    • Food Science and Preservation
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    • v.24 no.3
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    • pp.455-463
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    • 2017
  • In this study, the biological activities and physicochemical properties of polysaccharides from Gloiopeltis furcata were investigated. Polysaccharides were isolated by enzymes treatment (celluclast, flavourzyme, papain, termamyl, viscozyme) followed by ethanol precipitation and lyophilization. The yield of polysaccharides by enzymes treatment group were 52.8-66.4%. The major constituents in viscozyme treatment group were total sugar (71.04%), protein (7.22%), uronic acid (23.18 g/100 g), and sulfate (28.27%), respectively. The DPPH radical scavenging activity and ferric reducing antioxidant potential of the viscozyme treatment group at 5 mg/mL were 23.10% and $218.50{\mu}M$, respectively. The protective effects against $H_2O_2$-induced cytotoxicity in L132 cell of viscozyme treatment group at $1{\mu}g/mL$ was 85.64%. The viscozyme treatment group increased the production of nitric oxide (NO) in a dose-dependent manner. The antitumor activity of viscozyme treatment group (at $25{\mu}g/mL$) in A549, HeLa, SNU719 and MCF7 was 69.57%, 52.74%, 61.06% and 68.64%, respectively. All of data showed that the biological activities and chemical characteristics of enzymes treatment group are higher than that of the control group. The polysaccharides isolated from Gloiopeltis furcata investigated herein are useful as functional materials agents.