• Title/Summary/Keyword: 아폽토시스

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Apoptotic Effect of Proso Millet Grains on Human Breast Cancer MDA-MB-231Cells Is Exerted by Activation of BAK and BAX, and Mitochondrial Damage-mediated Caspase Cascade Activation (기장 종자 유래 추출물의 인간 유방암 MDA-MB-231 세포에 대한 세포독성에 관련된 미토콘드리아 손상-의존적 아폽토시스 유도 효과)

  • Do Youn Jun;Cho Rong Han;Young Ho Kim
    • Journal of Life Science
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    • v.33 no.1
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    • pp.15-24
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    • 2023
  • To examine the antitumor effect of proso millet grains, whether proso millet grains exert apoptotic activity against human cancer cells was investigated. When the cytotoxicity of 80% ethanol (EtOH) extract of proso millet grains was tested against various cancer cells using MTT assay, more potent cytotoxicity was observed against human breast cancer MDA-MB-231 cells than against other cancer cells. When the EtOH extract was evaporated to dryness, dissolved in water, and then further fractionated by sequential extraction using four organic solvents (n-hexane, methylene chloride, ethyl acetate, and n-butanol), the BuOH fraction exhibited the highest cytotoxicity against MDA-MB-231 cells. Along with the cytotoxicity, TUNEL-positive apoptotic nucleosomal DNA fragmentation and several apoptotic responses including BAK/BAX activation, mitochondria membrane potential (Δψm) loss, mitochondrial cytochrome c release into the cytosol, activation of caspase-8/-9/-3, and degradation of poly (ADP-ribose) polymerase (PARP) were detected. However, human normal mammary epithelial MCF-10A cells exhibited a significantly lesser extent of sensitivity compared to malignant MDA-MB-231 cells. Irrespective of Fas-associated death domain (FADD)-deficiency or caspase-8-deficiency, human T acute lymphoblastic leukemia Jurkat cells displayed similar sensitivities to the cytotoxicity of BuOH fraction, excluding an involvement of extrinsic apoptotic mechanism in the apoptosis induction. These results demonstrate that the cytotoxicity of BuOH fraction from proso millet grains against human breast cancer MDA-MB-231 cells is attributable to intrinsic apoptotic cell death resulting from BAK/BAX activation, and subsequent mediation of mitochondrial damage-dependent activation of caspase cascade.

Effect of Yonggak-san on the Immuno-regulatory and Apoptosis of Leukemia cells (용각산의 면역조절 및 백혈병세포의 아폽토시스에 미치는 효과)

  • Oh Chan Ha;Kwon Jin;Lee Kwang Gyu
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.16 no.5
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    • pp.932-937
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    • 2002
  • The purpose of this research was to investigate the effect of Yonggak-san (YGS) on the immune reaction and apoptosis of leukemia cells. Administration of YGS(500 mg/kg) enhanced proliferation of splenocytes, thymocytes and mesenteric lymph node cells, and also YGS accelerated subpopulation of splenic Band T, thymic T and mesenteric lymph node-T lymphocytes, especially significantly increased CD4+-TH cells in BALB/c mice. YGS accelerated phagocytic activity and production of nitric oxide in peritoneal macrophages. YGS induced apoptosis of transplanted-L1210 cells in vivo, increased apoptotic cell death of cultured-L1210 and/or Molt4 human leukemia cells, decreased of mitochondrial transmembrane potential of both cells in vitro. These results suggest that YGS have an immune-regulatory effect and anti-cancer property.

Preimplantation Development and Apoptosis of Mouse Embryos in the Medium Containing Extracellular Matrix (Extracellular Matrix 배지에서 생쥐 배아의 발생 및 아폽토시스)

  • Kang, Byung-Moon;Sohn, In-Pyo;Chung, Byung-Mok;Choi, Kyoo-Wan;Gye, Myung-Chan
    • Clinical and Experimental Reproductive Medicine
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    • v.27 no.3
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    • pp.253-259
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    • 2000
  • Objective: To verify the effect of Matrigel, a ECM complex from Engelbreth-Holm-Swarm (EHS) mouse sarcoma on the preimplantation development and apoptosis of mouse fertilized eggs. Method: Late pronucleus stage eggs were cultured through the blastocyst stage in the presence of Matrigel (0.5%, v/v). Characteristics of apoptosis and cell number assesed by Hoecst staining and TUNEL labeling at the blastocyst stage, respectively. Results: Morphological development, number of cells per embryo was significantly increased but rate and number of TUNEL positive nuclei of the embryo were decreased in the presence of Matrigel. Conclusion: This result suggested that at low concentration of Matrigel improves both viability and morphological development in the preimplantation mouse embryos.

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Expression of Expanded Polyglutamine Disease Proteins in Drosophila (Drosophila Polyglutamine Disease Models) (증가된 글루타민에 의해 초래되는 뇌신경질환의 초파리 모델에 대한 연구)

  • Shin, Sang Min;Paik, Kyung Hoon;Jin, Dong Kyu
    • Clinical and Experimental Pediatrics
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    • v.48 no.4
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    • pp.425-432
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    • 2005
  • Purpose : Polyglutamine diseases are a group of diseases caused by the expansion of a polyglutamine tract in the protein. The present study was performed to verify if polyglutamine disease transgenic Drosophila models show similar dysfunctions as are seen in human patients. Methods : Polyglutamine disease transgenic Drosophila were tested for their climbing ability. And using genetic methods, the effects of anti-apoptotic gene bcl-2 and chemical chaperones on neurodegeneration were observed. Also, spinocerebellar ataxia 2 (SCA2) transgenic Drosophila lines were generated for future studies. Results : Expanded forms of spinocerebellar ataxia 3 (SCA3) transgenic protein causes characteristic locomotor dysfunction when expressed in the nervous system of Drosophila but the anti-apoptotic gene bcl-2 shows no evidence of ameliorating the deleterious effect of the expanded protein. However, Glycerol, a chemical chaperone, seemed to reduce the toxicity, at least in the eyes of the transgenic flies. The level SCA2 expression is too weak in the transgenic SCA2 Drosophila for evaluation. Conclusion : SCA3 transgenic Drosophila show ataxic behavior as observed in human patients. Chemical chaperones such as glycerol may prove beneficial in this class of genetic disease, which has no current method of cure.

Effects of Orostachys japonicus A. Berger on the Immune System (와송(瓦松) 추출물이 면역체계에 미치는 영향)

  • Kwon, Jin;Han, Kwang-Soo
    • Korean Journal of Medicinal Crop Science
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    • v.12 no.4
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    • pp.315-320
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    • 2004
  • The purpose of this research was to investigate the effect of Orostachys japonicus A. Berger (OJB) on the immune system. Administration of OJB (500 mg/kg) enhanced viability of splenocytes and thymocytes in BALB/c mice, and also OJB increased of splenic T lymphocytes, significantly, increased CD4 positive $T_H$ cells and CD8 positive Tc cells. OJB markedly, enhanced the production of ${\gamma}-interferon$ in mice serum. OJB accelerated the apoptosis of L1210 and U937 leukemia cells and increased the expression of apoptosis-related ICE, c-myc, p53 gene. These results suggest that OJB have an immuno-regulatory and anti-cancer activity.

Anticarcinogenic Activity of Resveratrol, a Major Antioxidant Presnet in Red Wine : Induction of Apoptosis in Human Cancer Cells (적포도의 주 항산화물질, 레스베라트롤의 항암작용: 아폽토시스 의한 인체 암세포 사멸 유도)

  • 허연진;김정환;서효정;공구;서영준
    • Environmental Mutagens and Carcinogens
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    • v.19 no.1
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    • pp.56-62
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    • 1999
  • Resveratrol (3,5,4'-trihydroxy-trans-stilbene) has been considered to be as one of major antioxidants present in grapes responsible for beneficial effects of red wine consumption on coronary heart disease. This triphenolic stilbene has been suggested as a potential cancer chemopreventive agent based on its striking inhiitory effects on diverse cellular events associated with tumor initiation, promotion, and progression. The compound has strong antioxidative and anti-inflammatory activities which amy contribute to its chemopreventive/chemoprotective properties. In the present work, we have found that resveratrol reduces viability and DNA synthesis capability of cultured human promyelocytic leukemia (HL-60) cells. Likewise, the viability of human breast cancer cell line, MCF-7 was reduced by resveratrol treatment. The growth inhibitory and antiproliferative properties of resveratrol appear to be associated with its induction of apoptotic cell death as determined by morphological and ultrastructural changes, agarose gel electrphoretic analysis of internucleosomal DNA fragmentation, and in situ terminal end-labeling of fragmented DNA (TUNEL). This compound also inhibited the phorbol ester-induced expression of cyclooxygenase-2 (COX-2) protein in immortalized human mammary epithelial MCF-10A cells. These results suggest that resveratrol has the promising cancer therapeutic/chemopreventive potential.

ACTIVATION OF NF-$\kappa$B IN THE CISPLATIN-INDUCED APOPTOSIS OF ORAL SQUAMOUS CELL CARCINOMA (구강편평세포암종에서의 Cisplatin 유도 아폽토시스에서의 NF-$\kappa$B의 활성화)

  • Seo, Jong-Chun;Sung, Iel-Yong;Kim, Jong-Roul
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.32 no.2
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    • pp.94-100
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    • 2006
  • Purpose: This study was done to confirm the role of NF-$\kappa$B in cisplatin-induced apoptosis of oral squamous cell carcinoma. Materials and Methods: Five cell lines originated from different oral cancer patients were tested for the apoptosis by the treatment of cisplatin. These cells showed different degree of cisplatin-resistance and the order is OSCC-2>OSCC-3>OSCC-5> OSCC-1>OSCC-4. OSCC-2 and OSCC-4 cells were assayed for the apoptosis by measuring DNA fragmentation and TUNEL staining after cisplatin treatment. While OSCC-4 cells showed apoptosis, OSCC-2 cells showed no or very slight apoptosis by cisplatin treatment. Next, It was determined whether NF-$\kappa$B activation is required in mediating cisplatin-induced apoptosis of OSCC-4. Result: The result was that elevated NF-$\kappa$B activity mediated cisplatin-induced apoptosis. Conclusion: In conclusion, these findings suggest that NF-$\kappa$B activation is essential to cisplatin-induced apoptosis and it may be involved in cisplatin resistance in OSCC cells.

Induction of Apoptosis by Scolopendra subspinipes mutilans in Human Leukemia HL-60 Cells through Bcl-xL Regulation (왕지네(Scolopendra subspinipes mutilans)의 Bcl-xL 조절에 의한 HL-60 세포의 아폽토시스(Apoptosis) 유도)

  • Kim, Kil-Nam;Kim, Sang-Bum;Yoon, Weon-Jong;Yang, Kyoung-Sik;Park, Soo-Yeong
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.37 no.11
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    • pp.1408-1414
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    • 2008
  • The anticancer properties of Scolopendra subspinipes mutilans extract were investigated. The extract from S. subspinipes mutilans by 80% EtOH was fractionated with n-hexane, dichloromethan ($CH_2Cl_2$), ethylacetate (EtOAc), and butanol (BuOH) in order. The EtOAc fraction showed the highest inhibitory activity (about 80%) against human leukemia (HL-60) cell growth at $50\;{\mu}g/mL$. To explore the mechanism of cytotoxicity, we used several measures of apoptosis to determine whether these processes were involved in EtOAc fraction-induced HL-60 cell death. Our results showed EtOAc fraction induced cell shrinkage, cell membrane blebbing, apoptotic body, and DNA fragmentation. The EtOAc fraction gradually decreased the expression of anti-apoptotic Bcl-xL and led to the activation of caspase-3, -9 and cleavage of PARP. These findings suggest that S. subspinipes mutilans exhibits potential anticancer properties.

Anticarcinogenic Activity of a Novel Anthraquinone Derivative DHAQ-97: Induction of Apoptosis in Human Breast Cancer Cell Line MCF-7 (새로운 Anthraquinone 유도체, DHAQ-97의 항암작용: 아폽토시스에 의한 인체 유방암세포 사멸 유도)

  • 허연진;김정환;장정희;안병준;서영준
    • Environmental Mutagens and Carcinogens
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    • v.20 no.1
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    • pp.14-20
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    • 2000
  • DHAQ-97, (2-(3-[p-bis(2-chloroethyl)aminophenyl]-2 formylaminopropanoyloxy) methy1-1,4-dihy-droxy-9,10-anthraquinone), is a novel anthraquinone derivative synthesized for use as an anti-neoplastic agent. In the present study, we have evaluated the selective cytotoxicity of DHAQ-97 by comparing its effects on viability and proliferation of human breast cancer cell line (NCF-7) versus normal immortalized breast epithelial cell line (MCF-10A). Thus, DHAQ-97 reduced both viability and proliferation of MCF-7 cells to a much greater extent than did for MCF-10A cells. The growth inhibitory and anti-proliferative properties of DHAQ-97 appear to be attributable to its ability to induce apoptosis as revealed by positive staining after in 냐셔 nick-end labeling (TUNEL), cleavage of poly(ADP-ribose)polymerase, release of mitochondrial cytochrome c into cytoplasm, and increased expression of pro-apoptotic Bax protein. Recent studies have indicated possible involvement of the ubiquitous eukaryotic transcription factor, NF-kappa B (NF-kB) in the regulation of apoptotic cell death. In line induced cytotoxicity in cultured MCF-7 cells. Furthermore, mild activation of NF-kB, as determined by its increased DNA binding capability, was observed 30 min after treatment with 10$\mu\textrm{m}$ DHAQ-97. Taken together, the above findings suggest that DHAQ-97 exerts selective cytotoxicity towards cancer cells through induction of apoptosis, which appears to be regulated by NF-kB.

The Ethanol Extract of Red Ginseng Enhances Anti-Tumor Effects Using Co60 Gamma Irradiation (홍삼의 에탄올 추출물의 감마선 조사를 통한 항암효과 증대)

  • Hur, Jung-Mu;Kim, Dong-Ho
    • Journal of Applied Biological Chemistry
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    • v.54 no.1
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    • pp.15-20
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    • 2011
  • Red ginseng is one of the most popular traditional medicines in Korea. In this study, we developed a new technique in which ethanol extract of $\underline{r}$ed $\underline{g}$inseng (HRG) was exposed to the $Co^{60}$ gamma radiation ranging from 1~5 kGy. The irradiated HRG (IHRG) were analyzed by high performance liquid chromatography (HPLC) to determine any compositional changes of ginsenosides due to irradiation. No appreciable difference was observed in the HPLC pattern of ginsenosides of HRG. Using MTT assay, the cytotoxicity effect was significantly increased by IHRG compared to HRG. The $LD_{50}$ concentration was $30{\mu}g/mL$ for IHRG-1 (1 kGy), and $15{\mu}g/mL$ for IHRG-5 (5 kGy). The evidences of apoptosis, such as nuclei cleavage and Annexin V staining, were observed in the human prostate cancer PC-3 cells treated with the IHRG. Additionally, the level of reactive oxygen species (ROS) was apparently elevated by IHRG. We also studied the inhibitory effect of IHRG on the growth rate of tumor xenografts in BALB/c male mice. The tumor growth rates were inhibited by 56.9 and 76.1% in mice treated with 10 mg/kg of IHRG-1 and IHRG-5, respectively, compared with control group (21.1%). These results suggest that some biologically active and soluble components in HRG can be more effectively enhancement of anti-tumor effects using irradiation.