• Title/Summary/Keyword: DU-145

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Apoptosis-inducing Effect of Takrisodokyeum Extract in Androgen Independent Prostate Cancer Cells (남성호르몬 비의존형 전립선 암세포에서 탁리소독음(托裏消毒飮) 추출물의 세포고사 유도 효과)

  • Lee, Hyung-Jae;Kwon, Kang-Beom;Shin, Byung-Cheul;Kim, Eun-Kyung;Han, Mi-Jeong;Song, Mi-Young;Lee, Young-Rae;Park, Byung-Hyun;Ryu, Do-Gon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.4
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    • pp.861-865
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    • 2006
  • Takrisodokyeum (TRSDY) has been known to exert anti-tumoral activity in Korea. However, its molecular mechanism of action is not understood. In this study, we found that TRSDY induced apoptosis in androgen-independent prostate cancer DU145 cells as evidenced by DNA fragmentation and chromatine condensation in hoechst 33342 dye staining. Our data demonstrated that TRSDY-induced apoptotic cell death was accompanied by increases of PTEN and Par-4 in a time-dependent manner Taken together, these results suggest that TRSDY induce PTEN and Par-4 expression, and eventually lead to apoptotic cell death in androgen independent prostate cancer DU145 cells.

Different Expressions of HIF-$1\alpha$, Bcl-2 and Baxin DU145 Prostate Cancer Cells Transplanted in Nude Mouse between X-Ray and Neutron Irradiation (누드마우스에 주입된 DU-145 전립샘암에서 엑스선과 중성자선에 의한 HIF-$1\alpha$, Bcl-2, Bax 발현의 차이)

  • Kong, Moon-Kyoo;Kang, Jin-Oh;Kim, Sang-Ki;Shin, Dong-Oh;Park, Seo-Hyun;Kim, Chang-Ju;Chang, Hyun-Kyung
    • Radiation Oncology Journal
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    • v.27 no.4
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    • pp.218-227
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    • 2009
  • Purpose: To investigate the radiobiologic effects of neutron and X-ray irradiation on DU-145 prostate carcinoma cells by identifying the differences of HIF-$1\alpha$ expression and apoptosis. Materials and Methods: Nude mice were injected with the human prostate cancer cell line, DU-145, and then irradiated with 2 Gy and 10 Gy X-rays, or 0.6 Gy and 3.3 Gy neutrons, respectively. The mice were sacrificed at 24 hours and 120 hours after irradiation. The expression levels of HIF-$1\alpha$, Bcl-2 and Bax were compared with immunohistochemical staining and western blotting. The apoptotic indexes were compared with the Terminal deoxynucleotidyl biotin-dUTP nick and labeling (TUNEL) assay. Results: At day 1, HIF-$1\alpha$ and Bcl-2 expression decreased, while Bax expression and the number of TUNEL positive cells increased in neutron irradiated groups for the control and X-ray irradiated groups. The Bcl-2/Bax ratio was significantly lower in the neutron irradiated groups regardless of dose (p=0.001). The same pattern of the differences in the expressions of the HIF-$1\alpha$, Bcl-2, Bax, Bcl-2/Bax ratio, and apoptotic indexes were indentified at day 5. HIF-$1\alpha$ expression was related with Bcl-2 (p=0.031), Bax (p=0.037) expressions and the apoptotic indexes (p=0.016) at day 5. Conclusion: Neutron irradiation showed a decrease in HIF-$1\alpha$, Bcl-2 expression, and Bcl-2/Bax ratio, but increased Bax expression regardless of dose. This study suggests that the differences radiobiological responses between photon and neutron irradiation may be related to different HIF-$1\alpha$ expression and subsequent apoptotic protein expressions.

A New Histone Deacetylase Inhibitor, MHY4381, Induces Apoptosis via Generation of Reactive Oxygen Species in Human Prostate Cancer Cells

  • Richa, Sachan;Dey, Prasanta;Park, Chaeun;Yang, Jungho;Son, Ji Yeon;Park, Jae Hyeon;Lee, Su Hyun;Ahn, Mee-Young;Kim, In Su;Moon, Hyung Ryong;Kim, Hyung Sik
    • Biomolecules & Therapeutics
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    • v.28 no.2
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    • pp.184-194
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    • 2020
  • Histone deacetylase (HDAC) inhibitors represent a novel class of anticancer agents, which can be used to inhibit cell proliferation and induce apoptosis in several types of cancer cells. In this study, we investigated the anticancer activity of MHY4381, a newly synthesized HDAC inhibitor, against human prostate cancer cell lines and compared its efficacy with that of suberoylanilide hydroxamic acid (SAHA), a well-known HDAC inhibitor. We assessed cell viability, apoptosis, cell cycle regulation, and other biological effects in the prostate cancer cells. We also evaluated a possible mechanism of MHY4381 on the apoptotic cell death pathway. The IC50 value of MHY4381 was lower in DU145 cells (IC50=0.31 µM) than in LNCaP (IC50=0.85 µM) and PC-3 cells (IC50=5.23 µM). In addition, the IC50 values of MHY4381 measured in this assay were significantly lower than those of SAHA against prostate cancer cell lines. MHY4381 increased the levels of acetylated histones H3 and H4 and reduced the expression of HDAC proteins in the prostate cancer cell lines. MHY4381 increased G2/M phase arrest in DU145 cells, and G1 arrest in LNCaP cells. It also activated reactive oxygen species (ROS) generation, which induced apoptosis in the DU145 and LNCaP cells by increasing the ratio of Bax/Bcl-2 and releasing cytochrome c into the cytoplasm. Our results indicated that MHY4381 preferentially results in antitumor effects in DU145 and LNCaP cells via mitochondria-mediated apoptosis and ROS-facilitated cell death pathway, and therefore can be used as a promising prostate cancer therapeutic.

Cytotoxic Effect of Iljoong-eum on Human Prostate Cancer Cells (일중음의 인체 전립선암 세포에 대한 성장억제 효과)

  • Son, Gi-Jung;Park, Yang-Chun
    • The Journal of Internal Korean Medicine
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    • v.29 no.1
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    • pp.25-31
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    • 2008
  • Objectives : The study was intended to investigate whether Iljoong-eum (IJE) significantly affects proliferation and growth of prostate cancer cells. Materials and Methods : In vitro, after the treatment of DU-145 and PC-3 cells with IJE, we performed Sulforhodamine B (SRB) method. In vivo, a total of 8 male nude mice subcutaneously transplanted with the PC-3 cell line were divided in 2 groups. An experimental group was given IJE orally at a dose of 4.29ml/kg per day from the 8th to 31st day following tumor injection. All mice were observed for 31 days, and sacrificed by CO2 gas asphyxiation at the end of the experiment. The mean tumor volume and body weight of both groups were compared using Student's t-tests. Results : In vitro, IJE inhibited significantly proliferation and growth of DU-145 cells and PC-3 cells. In vivo, IJE inhibited significantly proliferation and growth of PC-3 cells xenografted into athymic nude mice. Conclusions : Our data has shown that IJE is effective in suppressing the growth rate of prostate cancer cells.

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Antioxidant and Anticarcinogenic Activities of Methanol Extracts from Soybean Products Fermented by Some Mycelia of Mushroom and $\textit{Bacillus megaterium}$ SMY-212 (버섯균사체 및 청국균 발효대두의 항산화능과 암세포 증식억제능)

  • Choi Jehun;Yang Hee-Sun;Shon Mi-Yae;Kim Jin-Soon;Park Seok-Kyu
    • Food Industry And Nutrition
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    • v.9 no.3
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    • pp.34-39
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    • 2004
  • 콩의 배당체 isoflavone류를 생리 활성형 aglycone으로 전환율을 증진시켜 콩 발효식품의 기능성을 증진시키고자, 식용버섯 균사체와 청국장 발효균 B. megateriw SMY-212를 이용하여 단독과 2단계 배양한 발효대두의 메탄올 추출물에 대한 항산화능과 인체 전립선암과 자궁암 세포주의 성장억제 효과를 조사하였다. 2단 발효대두 추출물의 수소공여능 효과는 1,000 $\mu$g/mL 농도에서 17.8∼26.9%로서 단독 발효대두보다 30∼40% 높았으며, 그 중에 동충하초와 SMY-212를 배양한 것이 가장 높았다. Linoleic acid에 대한 항산화 효과는 단독 발효대두는 동충하초가 가장 높았으며, 2단계 배양한 발효대두는 팽이균사체와 SMY-212가 오히려 높게 나타났다. 인체 전립선암 세포주(DU145)와 자궁암 세포주(Hela)에 대한 성장억제 효과는 단독배양에 서 모두 팽이버섯 균사체를 이용한 발효대두가 가장 높았으며, 2단계 배양에서 DU145에서는 팽이버섯과 아가리쿠스 균사체 배양물에 SMY-212를 이용한 발효대두가 높았고, HeLa에서는 팽이버섯, 동충하초, 새 송이버섯 균사체의 추출물 순으로 높았다. 결론적으로 삶은 콩에 버섯 균사체의 단독배양보다는 버섯균사체와 SMY-212를 2단 배양한 발효대두 추출물이 암세포주 성장억제 효과가 높게 나타났다.

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Effects of Mifepristone and Tamoxifen on Calcium Modulation in DU-145 Prostate Cancer Cells (DU-145 전립선 암세포에 있어서 mifepristone과 tamoxifen이 칼슘조절에 미치는 영향)

  • Kim, Yeo-Reum;Kim, Byeong-Gee
    • Journal of Life Science
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    • v.20 no.9
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    • pp.1324-1331
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    • 2010
  • Mifepristone (MIF) and Tamoxifen (TAM) have been used in the treatment of prostate cancer and breast cancer for more than a decade. MIF can induce apoptosis in both AR-positive and negative prostate cancer cells. Because of its pleiotropic ligand-receptor properties, TAM exerts cytotoxic activity in estrogen (ER)-positive and various ER.negative cancer cells. However, the molecular mechanisms of these two substances are not yet clear. In the present work, we report that the cytotoxic effects of MIF and TAM are due to the modulation of intracellular $Ca^{2+}$ level in DU-145, androgen-insensitive cells. When the cells were treated with micromolar concentrations of either MIF or TAM, the growth and viability were significantly decreased in a dose- and time-dependent manner. The apoptosis induced by MIF or TAM was further proved and analyzed by confocal laser scanning microscopy (CLSM) and fluorescence-activated cell sorting (FACS). In the cells cultivated in a normal 1.5 mM $Ca^{2+}$ medium, both MIF and TAM also induced an increase of the intracellular $Ca^{2+}$ level in a dose-dependent fashion. Since a change in calcium level could not be found in cells of the $Ca^{2+}$-free medium, the increase of intracellular $Ca^{2+}$ level might be due to an increase in extracellular calcium uptake. Our results show that the apoptotic effect was more prominent in TAM treatment compared to MIF treatment in DU-145 cells. The above findings might be due to the difference in the uppermost pathways of apoptosis induced by either MIF or TAM. When we checked the level of procaspase-8 activation, TAM showed minor level of activation, as opposed to MIF, which exerted strong activation. In both treatments, the levels of anti-apoptotic protein Bcl-2 decreased, and pro-apoptotic protein Bax level increased more than 2-fold. The activation of caspase-3, a key protease enzyme in the downstream pathway of apoptosis, was much higher in the cells treated with TAM, compared to the MIF treatment. The overall apoptotic activity shown in the present work was closely related to intracellular $Ca^{2+}$ concentration levels. Therefore, the cytotoxic activity induced by MIF and TAM might have been due to intracellular calcium modulation.

Anti-carcinogenic effects of non-polar components containing licochalcone A in roasted licorice root

  • Park, So Young;Kim, Eun Ji;Choi, Hyun Ju;Seon, Mi Ra;Lim, Soon Sung;Kang, Young-Hee;Choi, Myung-Sook;Lee, Ki Won;Yoon Park, Jung Han
    • Nutrition Research and Practice
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    • v.8 no.3
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    • pp.257-266
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    • 2014
  • BACKGROUND/OBJECTIVE: Licorice has been shown to possess cancer chemopreventive effects. However, glycyrrhizin, a major component in licorice, was found to interfere with steroid metabolism and cause edema and hypertension. The roasting process of licorice modifies the chemical composition and converts glycyrrhizin to glycyrrhetinic acid. The purpose of this study was to examine the anti-carcinogenic effects of the ethanol extract of roasted licorice (EERL) and to identify the active compound in EERL. MATERIALS/METHODS: Ethanol and aqueous extracts of roasted and un-roasted licorice were prepared. The active fraction was separated from the methylene chloride (MC)-soluble fraction of EERL and the structure of the purified compound was determined by nuclear magnetic resonance spectroscopy. The anti-carcinogenic effects of licorice extracts and licochalcone A was evaluated using a MTT assay, Western blot, flow cytometry, and two-stage skin carcinogenesis model. RESULTS: EERL was determined to be more potent and efficacious than the ethanol extract of un-roasted licorice in inhibiting the growth of DU145 and MLL prostate cancer cells, as well as HT-29 colon cancer cells. The aqueous extracts of un-roasted and roasted licorice showed minimal effects on cell growth. EERL potently inhibited growth of MCF-7 and MDA-MB-231 breast, B16-F10 melanoma, and A375 and A2058 skin cancer cells, whereas EERL slightly stimulated the growth of normal IEC-6 intestinal epithelial cells and CCD118SK fibroblasts. The MC-soluble fraction was more efficacious than EERL in inhibiting DU145 cell growth. Licochalcone A was isolated from the MC fraction and identified as the active compound of EERL. Both EERL and licochalcone A induced apoptosis of DU145 cells. EERL potently inhibited chemically-induced skin papilloma formation in mice. CONCLUSIONS: Non-polar compounds in EERL exert potent anti-carcinogenic effects, and that roasted rather than un-roasted licorice should be favored as a cancer preventive agent, whether being used as an additive to food or medicine preparations.

칼슘 및 협대역 측광 관측을 이용한 구상성단 NGC 6273의 항성종족 분석

  • Seo, Hyeon-Ju;Han, Sang-Il;No, Dong-Gu;Im, Dong-Uk;Lee, Yeong-Uk
    • The Bulletin of The Korean Astronomical Society
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    • v.37 no.2
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    • pp.145.2-145.2
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    • 2012
  • NGC 6273은 우리은하 중앙팽대부 영역에 위치하고 수평계열이 확장되어 있는 구상성단으로 초신성에 의해 중원소 함량이 증가된 2세대 종족의 존재가 의심되는 성단 중 하나이다. 이를 보다 면밀히 조사하고자 2011년 6월, 칠레에 위치한 Las Campanas Observatory의 2.5m Du Pont 망원경과 2K CCD를 이용하여 Ca, b, 그리고 y 필터로 측광 관측을 수행하였다. 중원소 함량에 민감하게 반응하는 hk (hk=(Ca-b)-(b-y)) 색지수로 색등급도를 그려본 결과 적색거성계열이 관측오차의 8배 이상으로 매우 넓게 퍼져있는 것을 발견하였다. 이러한 현상이 중원소 함량 차이로 인한 것인지, 아니면 성간소광효과나 배경별에 의한 영향인지를 분석하였고, 그 결과 중원소 함량의 차이가 있는 다중종족의 존재 가능성을 배재할 수 없음을 확인하였다. 이를 확인하기 위한 저해상도 분광관측이 진행되고 있으며, 이의 예비분석 결과를 아울러 발표할 예정이다.

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