• Title/Summary/Keyword: cytotoxic effects

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Anti-oxidative and Anti-cancer Activities of Methanol Extract of Machaerium cuspidatum (Machaerium cuspidatum 메탄올 추출물의 항산화 및 항암활성에 관한 연구)

  • Jin, Soojung;Oh, You Na;Park, Hyun-jin;Kwon, Hyun Ju;Kim, Byung Woo
    • Microbiology and Biotechnology Letters
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    • v.44 no.4
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    • pp.432-441
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    • 2016
  • Machaerium cuspidatum, a canopy liana, is a species of genus legume in the Fabaceae family and contributes to the total species richness in the tropical rain forests. In the present study, we investigated the antioxidative and anti-cancer effects of M. cuspidatum and its mode of action. The methanol extract of M. cuspidatum (MEMC) exhibited anti-oxidative activity with an $IC_{50}$ value of $1.66{\mu}g/ml$, and this was attributable to its 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity. MEMC also exhibited a cytotoxic effect and induced morphological changes in a dose-dependent manner in several cancer cell lines including human lung adenocarcinoma A549 cells, human hepatocellular carcinoma HepG2 cells, and human colon carcinoma HT29 cells. Moreover, MEMC treatment induced the accumulation of subG1 population, which is indicative of apoptosis in A549 and HepG2 cells. MEMC-induced apoptosis was confirmed by the increase in Annexin V-positive apoptotic cells and apoptotic bodies using Annexin-V staining and DAPI staining, respectively. Further investigation showed that MEMC-induced apoptosis was associated with the increase in p53 and Bax expression, and the decrease in Bcl-2 expression. In addition, MEMC treatment led to proteolytic activation of caspase-3, 8, and 9 and degradation of poly-ADP ribose polymerase (PARP). Taken together, these results suggest that MEMC may exert a beneficial anti-cancer effect by inducing apoptosis via both the extrinsic and intrinsic pathways in A549 and HepG2 cells.

Protective Effect of Antioxidants on the Reoxygenation Injury in Hypoxic Myocardium of Rat (저산소 심장의 산소 재공급에 따른 심근 손상에 있어서 항산화제의 보호 효과)

  • Yoon, Hyung-Ku;Lim, Jung-Kyoo;Kim, Myung-Suk
    • The Korean Journal of Pharmacology
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    • v.24 no.1
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    • pp.53-61
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    • 1988
  • The effect of antioxidants on the myocardial cellular damage which occurs during reoxygenation of hypoxic myocardium was examined in isolated rat hearts. The roles of oxygen free radical and lipid peroxidation in reoxygenation injury of myocardium were also investigated. In Langenorff preparation of isolated rat heart, which was made hypoxic by perfusion with the substrate free, hypoxic cardioplegic solution ($37^{\circ}C$, 90 min), the release of cytosolic enzymes (creatine phosphokinase, lactic dehydrogenase) and a lipid peroxidation product, malondialdehyde into the coronary effluent were abruptly increased by reoxygenation. The release of enzymes was closely parallel to that of MDA. These increases of enzymes and lipid peroxidation product were suppressed to various degrees in the presence of scavengers of superoxide anion (superoxide dismutase, 10,000 U), hydrogen peroxide (catalase, 25,000 U) and hydroxyl radical (dimethyl sulfoxide, 10%). A natural antioxidant, ${\alpha}-tocopherol$(4.5 uM) and a synthetic one, butylated hydroxytoluene (2 uM) suppressed the release of cytosolic enzymes with the concomittent reduction of lipid peroxidation as measured by malondialdehyde release into the coronary effluent. These effects of antioxidants were dose dependent, and were more pronounced when the antioxidants were administered throughout hypoxic and reoxygenation periods than given during reoxygenation period only. These results suggest that cytotoxic oxygen free radicals produced in the myocardium during reoxygenation may be responsible fur the myocardial cellular injury by enhancing the lipid peroxidation of cellular membranes. Furthermore, the antioxidants may exert protective effect against reoxygenation damage of hypoxic myocardium through the inhibition of lipid peroxidation reaction.

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Cyclophosphamide in the Treatment of Idiopathic UIP and NSIP (통상성 간질성 폐렴과 비특이성 간질성 폐렴의 치료에 있어 Cyclophosphamide의 역할)

  • Jeon, Kyeongman;Chung, Man Pyo;Shin, Sung-Chul;Yu, Chang Min;Koh, Won-Jung;Suh, Gee Young;Kim, Hojoong;Kwon, O Jung;Kim, Tae Sung;Lee, Kyung Soo;Han, Joungho
    • Tuberculosis and Respiratory Diseases
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    • v.55 no.2
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    • pp.175-187
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    • 2003
  • Background : Although corticosteroid and cytotoxic agent such as cyclophosphamide have been used for the treatment idiopathic interstitial pneumonia (IIP), efficacy of these toxic drugs are unclear because previous reports included the patients who did not undergo surgical lung biopsy and none evaluated the response according to histopathologic entities of IIP. To answer this, we retrospectively analyzed the treatment response and side effects of corticosteroids and cyclophosphamide therapy in patients with idiopathic UIP and NSIP. Methods : Among 61 patients with UIP and 26 patients with NSIP diagnosed by surgical lung biopsy at Samsung Medical Center from July 1996 to June 2002, those who received corticosteroid or cyclophosphamide therapy for at least 6 months and were followed for at least one year after the initiation of treatment were enrolled (32 UIP, 23 NSIP). Treatment response of 55 patients was assessed by ATS response criteria (clinical symptoms, pulmonary function test and radiological findings). Adverse reactions to either agent (42 cases of cyclophosphamide${\pm}$low-dose prednisolone, 49 cases of prednisolone alone) were also analyzed. Results : Irrespective of treatment regimen, NSIP showed more favorable response than UIP (6 months: 78.3% vs. 9.4%, 12 months: 69.6% vs. 9.4%, p<0.001). Cyclophosphamide showed comparable response to corticosteroid in NSIP while its efficacy was as poor as those of corticosteroid therapy in UIP. Significant adverse reaction to drug more frequently occurred in corticosteroid group (35.7%) than cyclophosphamide group (14.3%) (p=0.017). Conclusion : Cyclophosphamide is effective and more tolerable than corticosteroids in the treatment of idiopathic nonspecific interstitial pneumonia.

Detection of Multidrug Resistance Using Molecular Nuclear Technique (분자핵의학 기법을 이용한 다약제내성 진단)

  • Lee, Jae-Tae;Ahn, Byeong-Cheol
    • The Korean Journal of Nuclear Medicine
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    • v.38 no.2
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    • pp.180-189
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    • 2004
  • Although the outcome of cancer patients after cytotoxic chemotherapy is related diverse mechanisms, multidrug resistance (MDR) for chemotherapeutic drugs due to cellular P-glycoprotein (Pgp) or multidrug-resistance associated protein (MRP) is most important factor in the chemotherapy failure to cancer. A large number of pharmacologic compounds, including verapamil, quinidine, tamoxifen, cyclosporin A and quinolone derivatives have been reported to overcome MDR. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are available for the detection of Pgp and MRP-mediated transporter. $^{99m}Tc$-MIBI and other $^{99m}Tc$-radiopharmaceuticals are substrates for Pgp and MRP, and have been used in clinical studies for tumor imaging, and to visualize blockade of PgP-mediated transport after modulation of Pgp pump. Colchicine, verapamil and daunorubicin labeled with $^{11}C$ have been evaluated for the quantification of Pgp-mediated transport with PET in vivo and reported to be feasible substrates with which to image Pgp function in tumors. Leukotrienes are specific substrates for MRP and $N-[^{11}C]acetyl-leukotriene$ E4 provides an opportunity to study MRP function non-invasively in vivo. SPECT and PET pharmaceuticals have successfully used to evaluate pharmacologic effects of MDR modulators. Imaging of MDR and reversal of MDR with bioluminescence in a living animal is also evaluated for future clinical trial. We have described recent advances in molecular imaging of MDR and reviewed recent publications regarding feasibility of SPECT and PET imaging to study the functionality of MDR transporters in vivo.

Effect of Resveratrol on the Induction of Cdk Inhibitor p21 and Pro-apoptotic Bax Expression by amyloid-β in Astroglioma C6 Cells (신경교 세포에서 resveratrol이 amyloid-β에 의해 유도되는 Cdk inhibitor p21 및 Bax 발현의 감소 효과)

  • Kim Young Ae;Lim Sun-Young;Ko Woo Shin;Choi Byung Tae;Lee Yong Tae;Rhee Sook-Hee;Park Kun-Young;Lee Won-Ho;Choi Yung Hyun
    • Journal of Life Science
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    • v.15 no.2 s.69
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    • pp.169-175
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    • 2005
  • Resveratrol (3,4',5-trihydroxy-trans-stilbene), a phytoalexin found in grape skins, peanuts, and red wine, has been reported to have a wide range of biological and pharmacological properties. $Amyloid-\beta$ deposition and senile plaque-associated astrocytes are common neuropathological features of Alzheimer's disease. In this study, we have explored the effects of resveratrol on $amyloid-\beta-peptide-mediated$ cytotoxicity in vitro and modulation of cell growth-regulatory gene products in astroglioma C6 cells to elucidate its possible mechanism for anti-cytotoxicity. Exposure of C6 cells to $Amyloid-\beta$ resulted in dose-dependent growth inhibition and morphological changes of C6 cells, which were recovered by pre-treatment with resveratrol. The anti-proliferative effect of $amyloid-\beta$ was associated with the induction of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21 (WAF1/CIP1) expression assessed by RT-PCR and Western blot analysis in time-dependent manner in C6 cells. In addition, the pro-apoptotic Bax expression was also up-regulated in $amyloid-\beta-treated$ C6 cells without alteration of anti-apoptotic Bcl-2 and $Bcl-X_L$ expression. However, pre-treatment of resveratrol significantly inhibited $amyloid-\beta-induced$ p53, p21 and Bax levels, suggesting that the modulation of p53, p21 and Bax levels could be one of the possible pathways by which resveratrol functions as anti-cytotoxic agent. Our results demonstrate that resveratrol may enhance the protection against $amyloid-\beta-induced$ cytotoxicity by promoting the survival of glial cells.

Fermented Extracts of Korean Mistletoe with Lactobacillus (FKM-110) Stimulate Macrophage and Inhibit Tumor Metastasis (유산균으로 발효된 한국산 겨우살이 추출물의 Macrophage 자극에 의한 면역학적 활성화와 종양전이 억제효과)

  • Yoon, Taek-Joon;Yoo, Yung-Choon;Kang, Tae-Bong;Lee, Kwan-Hee;Kwak, Jin-Hwan;Baek, Young-Jin;Huh, Chul-Sung;Kim, Jong-Bae
    • Korean Journal of Food Science and Technology
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    • v.31 no.3
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    • pp.838-847
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    • 1999
  • Based on the results that the extract of Korean mistletoe (KM-110) has immunological and anti-tumor activities and its main component is lectin called KML-U, this study was carried out to investigate the immunostimulatory and anti-tumor activities of FKM-110, fermented KM-110 with lactobacillus, as a basic study for the development of functional food with anti-tumor activity. The amount of lectin after fermentation determined by ELISA was varied with the fermentation time and kinds of lactobacillus. Cytotoxic effects of FKM-110 on the various tumor cells was significant and dependent on the concentration of KML-U and the kinds of lactobacillus. FKM-110 stimulated macrophage and resulted in the secretion of some cytokines such as IL-1 and $IFN-{\gamma}$, but this effect was not correlated with the concentration of lectin. FKM-110 fermented with Marshall Lactobacillus casei showed the most potent antitumor activity in experimental and spontaneous metastasis models. When yoghurt produced with KM-110, Marshall Lactobacillus casei and skim milk was administered orally to mouse, the metastasis of tumor cells was significantly inhibited.

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The Physical and Chemical Properties and Cytotoxic Effects of Acer tegmentosum Maxim. Extracts (산겨릅나무 추출물의 이화학적 특성과 암세포 성장 억제 효과)

  • Shin, In-Cheol;Sa, Jae-Hoon;Shim, Tae-Heum;Lee, Jin-Ha
    • Applied Biological Chemistry
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    • v.49 no.4
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    • pp.322-327
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    • 2006
  • Food constituents analysis of Acer tegmentosum. Maxim.(Acer TM) stem was carried out according to AOAC method, and the antiradical activity on DPPH and cytotoxicity on human cell lines (AGS, HepG2, A549, MCF-7 and Chang) for the 80% ethylalcohol(EtOH) extracts of Acer TM stem were studied. The antiradical activity on DPPH radical of the ethylacetate(EtOAc) fraction of the bark showed a higher activity than that of $\alpha$-tocopherol, ascorbic acid and BHT. The inhibition activity of the 80% EtOH extracts from Acer TM stem on human cancer cell lines by SRB assay indicated a dose-dependent growth inhibition on most human carcinoma cells. The growth inhibition rate of each human cancer cell line showed 91.3% to AGS, 75.0% to A549, 74.1% to HepG2, and 70.2% to MCF-7 cells, respectively, when the 80% EtOH extract(1 mg/ml) of Acer TM stem was added.

Antioxidant and skin whitening effects of Inonotus obliquus methanol extract (차가버섯 메탄올 추출물의 항산화 및 미백효과)

  • Guk, Min-Hee;Kim, Dong-Ha;Lee, Chan;Jeong, Eun-Seon;Choi, Eun-Jae;Lee, Jae-Seong;Lee, Tae-Soo
    • Journal of Mushroom
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    • v.11 no.2
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    • pp.99-106
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    • 2013
  • This study was initiated to investigate the skin whitening activities of methanol extracts from fruiting bodies of I. obliquus. The total polyphenols and flavonoids contents of I. obliquus methanol extracts were 31.85 mg/g and 28.33 mg/g, respectively. The methanol extract of the mushroom treated on B16/F10 melanoma and NIH3T3 cell lines did not show cytotoxic activity. 2,2-diphenyl-1-picrylhydrazyl(DPPH) free radical scavenging activity and chelating activity on ferrous ions of I. obliquus methanol extract were lower than those of positive control, tocopherol and BHT. The tyrosinase and L-DOPA inhibitory activities of the extract were lower than those of positive control, kojic acid and ascorbic acid. The tyrosinase and melanin synthesis inhibitory activities of the melanoma cells treated with the extract were comparable with positive control, arbutin. The experimental results suggested that methanol extract of I. obliquus contained inhibitory activities of tyrosinase and melanin synthesis in the B16/F10 melanoma cells by dose dependent manner. High ultra-violet absorption spectra in the range of 280-350 nm showed that I. obliquus extract could protect skin from UV radiation damage. Therefore, fruiting bodies of I. obliquus can be used for developing skin whitening, anti-UV and skin care agents.

Physiological Activity and Nutritional Composition of Pleurotus Species (느타리속 버섯류의 영양성분 및 생리활성)

  • Um, Su-Na;Jin, Gyoung-Ean;Park, Kye-Won;Yu, Young-Bok;Park, Ki-Moon
    • Korean Journal of Food Science and Technology
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    • v.42 no.1
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    • pp.90-96
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    • 2010
  • In this study, the anti-oxidant, anti-tumorigenic, anti-hypertensive, anti-thrombic, anti-diabetic, and anti-inflammatory properties of 18 different species of genus Pleurotus were investigated. In addition, the amino acid, $\beta$-glucan, and polyphenol content were also measured. All species contained more than 20 mg% of polyphenol with the highest contents found in Pleurotus cornucopiae var. citrinopileatus (yellow pleurotus) ($39.13{\pm}0.82\;mg%$). The $\beta$-glucan contents was also the highest in yellow Pleurotus ($37.67{\pm}0.22%$) followed by Won-Hyeong1 (C, $28.75{\pm}0.61%$) and Jang-an PK (A, $27.95{\pm}0.33%$). The yellow Pleurotus exhibited the highest antioxidant activity as assessed by the DPPH scavenging rate with an $IC_{50}$ value of $2.94{\pm}0.44\;mg/mL$. Ethanol extracts from the yellow Pleurotus treated at 1% concentration showed cytotoxic activity up to 36.9% in the human embryonic kidney 293T cell lines. The yellow Pleurotus also showed the highest inhibitory effects on ACE activity ($60.52{\pm}0.2%$). Finally, the yellow Pleurotus exhibited anti-diabetic and anti-inflammatory properties as shown by inhibition of $\alpha$-amyloglucosidase activity ($50.5{\pm}0.8%$) and nitric oxide production ($68.4{\pm}0.3%$). Taken together, our data indicate the yellow pleurotus is a promising functional food ingredients.

Cytotoxic Effects of Prevotella nigrescens on Cultured Cells (Prevotella nigrescens가 배양된 세포에 미치는 영향)

  • Han, Jin-Soon;Kim, Eun-Sook;Lee, Su-Jong;You, Yong-Ouk;Han, Kyung-Soo;Im, Mi-Kyung
    • Restorative Dentistry and Endodontics
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    • v.27 no.2
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    • pp.183-195
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    • 2002
  • 흑색 색소를 형성하는 그람음성 혐기성 세균은 급성 임상 증상을 가진 환자의 근관에서 자주 발견되는 세균으로서 세균 및 세균의 성분과 산물이 치근단 병소의 생성과 밀접하게 연관된 것으로 알려져 있다. 본 연구는 흑색 색소를 형성하는 그람음성 혐기성 세균 중 가장 발현율이 높은 Prevotella nigrescens가 배양된 세포에 미치는 세포 독성을 연구하고자 하였다. 두 가지 세포주 및 사람의 치은섬유모세포를 일차배양하여 사용하였으며, 세포주에 따른 독성 발현에 차이가 있는지를 비교하였다. P. nigrescens ATCC 33563 표준 균주 및 임상 균주로는 환자의 감염된 근관으로부터 165 rRNA primer를 사용한 중합효소 연쇄반응으로 P. nigrescens 6 균주를 동정하여 사용하였다. 세균배양액, 세균의 초음파 추출단백질 및 lipopolysaccharide (LPS)를 MC3T3-El 조골세포, NIH3T3 섬유모세포 및 치은섬유모세포에 첨가한 후 MTT분석법으로 세포의 활성을 측정하였으며, 세포의 형태학적 변화를 도립현미경으로 관찰하였다. 세균배양액을 100$\mu\textrm{l}$ 첨가한 경우는 세가지 세포주 모두에서 통계적으로 유의하게 세포의 활성을 억제하였다. 세균의 초음파 추출단백질 12.5$\mu\textrm{g}$/ml 와 25$\mu\textrm{g}$/ml 는 NIH3T3세포에 통계적으로 유의한 세포독성을 보였다. 세 가지 세포주에 대한 LPS의 세포 독성 효과는 첨가된 LPS의 농도 및 균주에 따라 다양하게 나타났다. 심하게 손상된 세포는 세포의 단일층이 수축되고 세포가 응집되었으며 세포가 배양용기의 바닥에서 떨어지는 양상이 도립 현미경하에서 관찰되었다. 본 연구의 결과 P. nigrescens가 숙주 반응을 조절하여 치수 및 치근단 병소의 유발 및 악화에 기여하는 세균으로 작용할 수 있음을 시사한다. 조직과 함께 제거하고 포르말린에서 48시간 고정시킨 후 파라핀에 포매한 다음에 micro-tome을 사용하여 6$\mu\textrm{m}$로 serial section을 시행하였다. 정중선 부위의 시편에 Hematoxylin-Eosin staining을 시행한 후 Olsson, Orstavik 그리고 Mjor 등의 방법에 따라 조직학적 변화를 관찰한 후 slight(1), moderate(2), severe inflammation(3)의 단계로 분류하였다. 얻어진 결과를 통계처리 프로그램인 Jandel사의 Sigmastat을 이용하여 Kruskal Wallis Test로 통계처리를 하였다. 결과 : (Table omitted) 결론 : 1) Pulp Canal Sealer를 제외한 모든 군에서 시간이 지남에 따라 유의성 있게 염증이 감소되는 양상을 보였다(p<0.05). 2) Pulp Canal Sealer는 1주, 2주, 12주에서 강한 염증반응을 보였다. 3) AH 26과 AH Plus에서는 1주, 2주에서 강한 염증반응을 보였으나 12주에서는 염증반응이 감소하였다. 4) 새로 개발된 봉함제 Adseal-1,2는 1주, 2주에서는 가장 약한 염증반응을 보이나 4주, 12주 후에는 AH Plus와 비슷한 수준의 염증 반응을 보였다. 5) Pulp Canal Sealer를 제외한 모든 군에서 인정할 만한 생체친화성을 보였다. 6) Adseal-2가 Adseal-1에 비하여 전반적으로 낮은 염증반응을 보였다. 7) 각 군간 결과의 차이에 통계적 유의성은 없었다(p>0.05).mmunity. Then, a hierarchical language is to defeat its own purpose.중 행정부가 북한에 대해 실시한 포용정책이 어떠한 성과를 거두고 어떠한 문제점을 간과하고 있는가에 대해 논의하고, 대북 정책의 새로운 지평을 논의하는 것을 목적으로 하고 있다. 1) 포용 정책은 세계의