• 제목/요약/키워드: Bcl2-A1

검색결과 859건 처리시간 0.028초

Liver Kinase B1 Mediates Its Anti-Tumor Function by Binding to the N-Terminus of Malic Enzyme 3

  • Seung Bae Rho;Hyun Jung Byun;Boh-Ram Kim;Chang Hoon Lee
    • Biomolecules & Therapeutics
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    • 제31권3호
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    • pp.330-339
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    • 2023
  • Liver kinase B1 (LKB1) is a crucial tumor suppressor involved in various cellular processes, including embryonic development, tumor initiation and progression, cell adhesion, apoptosis, and metabolism. However, the precise mechanisms underlying its functions remain elusive. In this study, we demonstrate that LKB1 interacts directly with malic enzyme 3 (ME3) through the N-terminus of the enzyme and identified the binding regions necessary for this interaction. The binding activity was confirmed to promote the expression of ME3 in an LKB1-dependent manner and was also shown to induce apoptosis activity. Furthermore, LKB1 and ME3 overexpression upregulated the expression of tumour suppressor proteins (p53 and p21) and downregulated the expression of antiapoptotic proteins (nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and B-cell lymphoma 2 (Bcl-2)). Additionally, LKB1 and ME3 enhanced the transcription of p21 and p53 and inhibited the transcription of NF-κB. Moreover, LKB1 and ME3 suppressed the phosphorylation of various components of the phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B signaling pathway. Overall, these results suggest that LKB1 promotes pro-apoptotic activities by inducing ME3 expression.

차가버섯 추출물에 의한 신경교모세포종 U-87 MG 세포의 증식 억제 효과 (Inhibition Effect of Cell Proliferation and Apoptosis by Inonotus obliquus in Human Glioblastoma U-87 MG Cells)

  • 신정아;박주현;김선희;송관영
    • 한국식품영양과학회지
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    • 제42권7호
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    • pp.1022-1028
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    • 2013
  • 러시아에서 여러 민간요법으로 사용되어지고 있는 차가버섯은 대장암, 위암 등에서 항암효능이 있다고 알려져 있다. 그러나 뇌종양에 대한 연구는 현재 이루어지지 않고 있으며 차가버섯의 항암 효능에 대한 기전 연구도 미미한 실정이다. 따라서 본 연구에서는 신경교모세포종 U-87 MG 세포주에 대한 성장억제 효과를 확인하고자 세포생존율 변화와 형태학적 변화, 세포주기에 미치는 영향과 세포사멸 관련 단백질 및 세포주기 조절 단백질의 발현 변화를 조사하였다. 그 결과 차가버섯 추출물을 처리한 U-87 MG 세포 생존율이 유의하게 감소하였으며, Bcl-2, Bax와 p-p53 단백질 수준차이는 없었고 caspase-3 활성에 영향을 미쳐 죽음 수용체 경로에 의한 세포사멸이 이루어졌다. 또한 세포주기를 관찰한 결과 $G_0/G_1$ 세포주기에서 성장 억제를 확인하였으며, 이는 cyclin D1, CDK2 단백질 발현량의 감소와 RB 단백질의 인산화 억제 때문이라는 결론에 도달하였다. 본 연구결과는 차가버섯을 뇌종양의 치료 및 보조제로서 역할을 수행할 수 있을 것으로 사료된다.

A549 폐암 세포주에 대한 정력대조사폐탕 및 정력탕의 Apoptosis 효과 (Apoptotic Effects of Junglyeokdaejosape-tang and Junglyeok-tang on A549 lung Cancer Cells)

  • 유병길;김명동;황태준;유영민;이선구
    • 동의생리병리학회지
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    • 제19권5호
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    • pp.1204-1212
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    • 2005
  • Lung cancer is one of the common malignant tumors in the world. It occurs more increasingly due to the serious air pollution, heavy smoking, expoure to ionized radiation, pollution with heavy metal, and owing to well advanced diagnostic skill, etc. Also lung cancer has the limitation of medical care because metastasis is already shown up in more than half cases when it is first detected through medical examination. Although it is treated with chemoradiation, the rate of deaths from lung cancer is high as well, because blood has a lot of toxicity which give side effects. So it has a low rate of cure. So, the ways of various treatment is being researched to raise the rate of care and decrease the side effects recently, and one of the results is inducing apoptosis which makes use of molecularbiologic diagnosis of lung cancer's cell and using oriental medicine drugs. The purpose of this study is whether apoptosis would happen on the human lung carcinoma cell by treated with Junglyeokdaejosape-tang, Junglyeok-tang Junglyeokdaejosape-tang and Junglyeok-tang has been prescribed for cough, chest pain, and many other similar cases. Cough and chest pain is shown in early lung cancer. That is why we used these prescriptions. Apoptosis happend on the human lung carcinoma A549 cells treated with Jeongiyeokdaejosapye-tang, Jeonglyeok-tang. The concentration-dependent inhibition of cell viability was observed and apoptosis was confirmed by DNA fragmentation. Bcl-2 and COX-2 mRNA expression decreased, but Bax mRNA expression increased, so it was identified with the case of indomethacin known to enhance apoptotic DNA fragmentation. Also expression of the p21, p53, cyclin E, cyclin D1, cytochrome c, caspase-3, and caspase-9 protein increased and the activity of caspase-3 increased, as well. Last, fragmentation of the PARP was shown. The previous and present results indicated that apoptosis of A549 cells by above-mentioned drugs is associated with the blockage of G1/S progression.

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

  • 김여름;김병기
    • 생명과학회지
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    • 제20권9호
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    • pp.1324-1331
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    • 2010
  • Mifepristone (MIF)와 Tamoxifen (TAM)은 각각 전립선암과 유방암치료제로 오랫동안 사용되고 있다. MIF는 안드로겐수용체(AR) 양성인 세포와 음성이 세포 모두에서 세포사멸을 유도하며, TAM 은, 리간드-수용체작용 기작의 다양한 특성에 의하여 에스트로겐(ER) 양성인 세포뿐 만 아니라 다른 종류의 암세포에서도 세포사멸을 유도하는 것으로 알려져 있다. 본 연구에서는 AR 음성인 DU-145 전립선암세포에 있어서, MIF와 TAM의 세포독성이 세포 내 칼슘농도 변화에 기인된 세포사멸기작에 의한 것임을 보여준다. MIF와 TAM을 처리시 세포성장은 농도와 시간의존적으로 감소하였으며, confocal laser scanning microscopy (CLSM)과 fluorescence-activated cell sorting (FASC)로 세포를 분석한 결과 각각 MIF와 TAM을 2일간 처리한 세포에서 세포사멸이 진행되는 것을 관찰하였다. 세포독성효과를 비교했을 경우, TAM이 MIF 보다 강하게 작용하였다. MIF와 TAM을 처리한 세포 내 칼슘변화 측정 시, 칼슘농도 또한 처리 약물의 농도와 시간 의존적으로 증가하였다. 1.5 mM 칼슘배지와 칼슘제거된 배지에서의 실험결과를 비교한 바, 세포 내 칼슘증가는 외부로부터의 유입에 의한 것으로 생각된다. 세포독성효과와 마찬가지로 칼슘증대 효과 역시 TAM에서 뚜렷하게 나타났다. 수용체 매개 세포사멸기작의 초기에 관여하는 procaspase-8은 MIF 처리 시 뚜렷이 활성화 되었으나, TAM의 경우 활성화가 MIF의 경우에 비해 강하지 못하였다. 그러나, 세포사멸의 중추적인 역할을 하는 caspase-3은 TAM 을 처리한 세포에 있어서 활성 정도가 훨씬 높았다. 세포사멸과정의 중요한 조절 단백질인 Bcl-2 그룹단백질의 발현을 조사해 본 결과, 세포사멸 억제단백질인 Bcl-2의 발현은 MIF, TAM 처리 시 동일하게 감소한 반면, 촉진단백질인 Bax의 발현은 2-3배 가량 증대되었다. 이상의 결과로 보아 MIF와 TAM은 세포 내 칼슘조절을 통하여 세포사멸을 유도하나, 세포사멸의 초기단계는 MIF와 TAM이 서로 다른 경로를 경유할 가능성이 있는 것으로 생각된다.

혈관내피성장인자에 관한 고찰 (Review of Vascular Endothelial Growth Factor)

  • 김석범;김동현;송주영;김진상
    • The Journal of Korean Physical Therapy
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    • 제14권1호
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    • pp.219-226
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    • 2002
  • Vascular endothelial growth factors(VEGFs) constitute a group of structurally and functionally related growth factor that modulate many important physiological functions of endothelial cells, especially angiogenesis. This paper explain substance, which participate in signaling transduction of VEGF, including Bcl-2, caspase, focal adhesion kinase(FAK), integrin ${\alpha}v{\beta}3$, MAP kinase, nitric oxide(NO)and prostacyclin(PGI2). Physical therapy enhance angiogenesis for repairment of injury which as wound healing, muscle contusion, cerebrovascular disease, rheumatoid arthritis. Therefore this review assist understanding for mechanism of physical therapy as therapeutic angiogenesis.

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HT-29 인체 대장암 세포에서 검정콩 된장의 in vitro 항암 효과 (Anticancer Effects of Black Soybean Doenjang in HT-29 Human Colon Cancer Cells)

  • 박의성;이재양;박건영
    • 한국식품영양과학회지
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    • 제44권9호
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    • pp.1270-1278
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    • 2015
  • 시료 된장의 pH, 아미노태, 암모니아태 수치는 각 군 간 특별한 차이는 보이지 않았다. 검정콩 된장이 가장 높은 폴리페놀 농도, DPPH를 이용한 항산화 효과를 보였다. 된장 추출물은 0.1~0.5 mg/mL 범위까지는 RAW 264.7 cells의 증식을 억제하지 않았으며, HT-29를 이용한 MTT에서 BD 군이 가장 높은 암세포 성장 억제율을 보였다. HT-29에서 pro-inflammatory cytokine인 $TNF-{\alpha}$, IL-6와 염증관련 인자 COX-2의 mRNA 발현은 시료 처리군에서 대조군에 비해 낮은 수치를 나타냈으며 BD군에서 가장 낮은 수치를 보였다(P<0.05). 세포 증식에 관여하는 p21, p53과 cyclin D1의 mRNA 발현은 p21과 p53가 BD군에서 발현이 증가하였고, cyclin D1은 BD군에서 낮아졌다. Apoptosis 관련 유전자인 Bcl-2는 BD군이 가장 낮은 발현을 보였다. 이상의 결과로 BD군은 CD, SD군에 비해 높은 폴리페놀 농도, 항산화 효과, 대장암세포에서 pro-inflammatory cytokines과 세포 증식에 관여하는 유전자 등을 조절한다. 이 결과는 아마도 서목태 된장의 높은 총 페놀화합물의 양과 안토시아닌의 함량으로 얻어진 결과로 생각된다.

Protective Effect of BOEC Co-Culture System against Nitric Oxide on Development of Bovine IVM/IVF Embryos

  • Jang, Hyun-Yong;Jung, Yu-Sung;Li, Zheng-Yi;Yoon, Hyoung-Jong;Cheong, Hee-Tae;Kim, Jong-Taek;Park, Choon-Keun;Yang, Boo-Keun
    • Reproductive and Developmental Biology
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    • 제32권3호
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    • pp.167-173
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    • 2008
  • Somatic cells such as oviduct epithelial cell, uterine epithelial cell, cumulus-granulosa cell and buffalo rat river cell has been used to establish an effective culture system for bovine embryos produced in in vitro. But nitric oxide (NO) metabolites secreted from somatic cells were largely arrested the development of bovine in vitro matured/ in vitro fertilized (IVM/IVF) embryos, suggesting that NO was induced the embryonic toxic substance into culture medium. The objective of this study was to investigate whether BOEC co-culture system can ameliorate the NO-mediated oxidative stress in the culture of bovine IVM/IVF embryos. Therefore, we evaluated the developmental rate of bovine IVM/IVF embryos under BOEC co-culture system in the presence or absence of sodium nitroprusside (SNP), as a NO donor, and also detected the expression of growth factor (TGF-$\beta$, EGF and IGFBP) and apoptosis (Caspase-3, Bax and Bcl-2) genes. The supplement of SNP over 5 uM was strongly inhibited blastocyst development of bovine IVM/IVF embryos than in control and 1 uM SNP group (Table 2). The developmental rates beyond morulae stages of bovine IVM/IVF embryos co-cultured with BOEC regardless of SNP supplement (40.4% in 5 uM SNP+ BOEC group and 65.1% in BOEC group) were significantly increased than those of control (35.0%) and SNP single treatment group (23.3%, p<0.05: Table 3). The transcripts of Bax and Caspase-3 genes were detected in all experiment groups (1:Isolated fresh cell (IFC), 2:Primary culture cell (PCC), 3:PCC after using the embryo culture, 4: PCC containing 5 uM SNP and 5: PCC containing 5 uM SNP after using the embryo culture), but Bcl-2 gene was not detected in IFC and PCC (Fig. 1). In the expression of growth factor genes, TGF-$\beta$ gene was found in all experimental groups, and EGF and IGFBP genes were not found in IFC and PCC (Fig. 2). These results indicate that BOEC co-culture system can increase the development beyond morula stages of bovine IVM/IVF embryos, possibly suggesting the alleviation of embryonic toxic substance like nitric oxide.

Effects of Trichostatin A and 5-aza-2'deoxycytidine on Nuclear Reprogramming in Pig Cloned Embryos

  • Lee, Sung Hyun;Xu, Yong-Nan;Heo, Young-Tae;Cui, Xiang-Shun;Kim, Nam-Hyung
    • Reproductive and Developmental Biology
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    • 제37권4호
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    • pp.269-279
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    • 2013
  • Low efficiency of somatic cell nuclear transfer (SCNT) is attributed to incomplete reprogramming of transfered nuclei into oocytes. Trichostatin A (TSA), histone deacetylase inhibitor and 5-aza-2'deoxycytidine (5-aza-dC), DNA methylation inhibitor has been used to enhance nuclear reprogramming following SCNT. However, it was not known molecular mechanism by which TSA and 5-aza-dC improve preimplantation embryo and fetal development following SCNT. The present study investigates embryo viability and gene expression of cloned porcine preimplantation embryos in the presence and absence of TSA and 5-aza-dC as compared to embryos produced by parthenogenetic activation. Our results indicated that TSA treatment significantly improved development. However 5-aza-dC did not improve development. Presence of TSA and 5-aza-dC significantly improved total cell number, and also decreased the apoptotic and autophagic index. Three apoptotic-related genes, Bak, Bcl-xL, and Caspase 3 (Casp3), and three autophagic-related genes, ATG6, ATG8, and lysosomal-associated membrane protein 2 (LAMP2), were measured by real time RT-PCR. TSA and 5-aza-dC treatment resulted in high expression of anti-apoptotic gene Bcl-xL and low pro-apoptotic gene Bak expression compared to untreated NT embryos or parthenotes. Furthermore, LC3 protein expression was lower in NT-TSA and NT-5-aza-dC embryos than those of NT and parthenotes. In addition, TSA and 5-aza-dC treated embryos displayed a global acetylated histone H3 at lysine 9 and methylated DNA H3 at lysine 9 profile similar to the parthenogenetic blastocysts. Finally, we determined that several DNA methyltransferase genes Dnmt1, Dnmt3a and Dnmt3b. NT blastocysts showed higher levels Dnmt1 than those of the TSA and 5-aza-dC blastocysts. Dnmt3a is lower in 5-aza-dC than NT, NTTSA and parthenotes. However, Dnmt3b is higher in 5-aza-dC than NT and NTTSA. These results suggest that TSA and 5-aza-dC positively regulates nuclear reprogramming which result in modulation of apoptosis and autophagy related gene expression and then reduce apoptosis and autophagy. In addition, TSA and 5-aza-dC affects the acetylated and methylated status of the H3K9.

자가식세포작용: 천연물항암제로서의 신규작용기전 (Autophagy: Noble target mechanisms in natural medicines as anticancer agents)

  • 강세찬
    • Journal of Plant Biotechnology
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    • 제37권1호
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    • pp.57-66
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    • 2010
  • Programmed cell death systems are important for an active type of cell deaths. Among them, a type of programmed cell death, autophagy is activated in cancer cells in response to multiple stresses and has been demonstrated to promote tumor cell survival and drug resistance. Thus, in the area of cancer, over the time frame form around the 1940s to date, of the 155 small molecules, 73% are other than "synthetic", with 47% actually being either "natural products" or "directly derived therefrom". Autophagy has multiple physiological functions in multicellular organisms, including protein degradation and organelle turnover. Genes and proteins that constitute the basic machinery of the autophagic process were first identified in the yeast system and some of their mammalian orthologues have been characterized as well. Numerous oncogenes, including Akt1, Bcl-2, NF1, PDPK1, class I PI3K, PTEN, and Ras and oncosuppressors, inculuding Bec-1, Bif-1, DAPK-1, p53 and UVRAG suppress or promote the autophagy pathway. Regulation of autophagy in tumors is governed by similar principles of the normal cells, only in a much more complicated manner, given the frequently observed abnormal PI3K activation in cancer and the multitude of interactions between the PI3K/AKT/mTOR pathway and other cell signaling cascades, often also deregulated in tumor cells. Autophagy induction by some anticancer agents underlines the potential utility of its induction as a new cancer treatment modality of development for natural medicines.

Neuroprotective Effect of β-Lapachone in MPTP-Induced Parkinson's Disease Mouse Model: Involvement of Astroglial p-AMPK/Nrf2/HO-1 Signaling Pathways

  • Park, Jin-Sun;Leem, Yea-Hyun;Park, Jung-Eun;Kim, Do-Yeon;Kim, Hee-Sun
    • Biomolecules & Therapeutics
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    • 제27권2호
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    • pp.178-184
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    • 2019
  • Parkinson's disease is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons within the substantia nigra pars compacta. In the present study, we investigated whether ${\beta}-Lapachone$ (${\beta}-LAP$), a natural naphthoquinone compound isolated from the lapacho tree (Tabebuia avellanedae), elicits neuroprotective effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mouse model. ${\beta}-LAP$ reduced the tyrosine hydroxylase (TH)-immunoreactive fiber loss induced by MPTP in the dorsolateral striatum, and alleviated motor dysfunction as determined by the rotarod test. In addition, ${\beta}-LAP$ protected against MPTP-induced loss of TH positive neurons, and upregulated B-cell lymphoma 2 protein (Bcl-2) expression in the substantia nigra. Based on previous reports on the neuroprotective role of nuclear factor-E2-related factor-2 (Nrf2) in neurodegenerative diseases, we investigated whether ${\beta}-LAP$ induces upregulation of the Nrf2-hemeoxygenae-1 (HO-1) signaling pathway molecules in MPTP-injected mouse brains. Western blot and immunohistochemical analyses indicated that ${\beta}-LAP$ increased HO-1 expression in glial fibrillary acidic protein-positive astrocytes. Moreover, ${\beta}-LAP$ increased the nuclear translocation and DNA binding activity of Nrf2, and the phosphorylation of upstream adenosine monophosphate-activated protein kinase (AMPK). ${\beta}-LAP$ also increased the localization of p-AMPK and Nrf2 in astrocytes. Collectively, our data suggest that ${\beta}-LAP$ exerts neuroprotective effect in MPTP-injected mice by upregulating the p-AMPK/Nrf2/HO-1 signaling pathways in astrocytes.