• 제목/요약/키워드: Cyclin E1

검색결과 171건 처리시간 0.023초

인체폐암세포에서 Bcl-2 발현저하 및 caspase 활성을 통한 청조구폐탕의 apoptosis 유발에 관한 연구 (Apoptosis of Human Lung Carcinoma Cells through the Inhibition of Bcl-2 Expression and Activation of Caspase by Chungjogupae-tang)

  • 조인주;감철우;김기탁;박동일
    • 동의생리병리학회지
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    • 제21권1호
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    • pp.93-97
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    • 2007
  • We previously reported the anti-proliferative effect of Chungjogupae-tang (CJGPT) in human lung carcinoma A549 cells, which was associated with the induction of cyclin-dependent kinase inhibitor p21 in a tumor suppressor p53-independent manner. CJGPT treatment also resulted in the inhibition of prostaglandin E2 release A549 cells by the down-regulation of cyclooxygenase-2. In the present study, we investigated the pathway of the induction of apoptotic cell death by CJGPT in A549 cells. It was found that CJGPT could inhibit the cell viability and induce the apoptotic cell death of A549 cells in a dose-dependent manner as measured by hemocytometer counts, flow cytometry analysis and agarose gel electrophoresis. Apoptosis of A549 cells by CJGPT was associated with a down-regulation of anti-apoptotic Bcl-2 and inhibitor of apoptosis proteins (IAPs) expression. Additionally, DNA fragmentation by CJGPT was connected with the activation of inhibitor of caspase-activated DNase/DNA fragmentation factor 45 (ICAD/DFF45) protein expression.

Overexpression of Periostin Protein in Non-Small Cell Lung Carcinoma is Not Related with Clinical Prognostic Significance

  • Park, Won-Young;Shin, Dong-Hoon;Kim, Jae-Ho;Lee, Min-Ki;Lee, Ho-Seok;Lee, Chang-Hun
    • Tuberculosis and Respiratory Diseases
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    • 제72권2호
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    • pp.132-139
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    • 2012
  • Background: Periostin is preferentially expressed in periosteum, indicating a potential role in bone formation. Recently, there have been emerging controversies about its role in invasion and metastasis of human malignancies. We attempted to determine the clinicopathological significance of periostin expression in non-small cell lung carcinoma (NSCLC). Methods: Immunohistochemical staining of periostin protein from 91 cases of NSCLCs was performed using tissue microarray blocks. The results were correlated with clinicopathological parameters. Results: Positive reaction to periostin was predominantly noted in the tumor stroma. The strongest reaction presented as a band-like pattern just around the tumor nests. Non-neoplastic lung tissue and most in-situ carcinomas did not show a positive reaction in their stroma. With respect to tumor differentiation, moderate to poor differentiated tumors (47/77) revealed even higher periostin expression than the well-differentiated ones (4/14) (p=0.024). High periostin expression was positively correlated with E-cadherin and p53 expression, but was not related with patient age, sex, tumor type, PCNA index, b-catenin, cyclin D1, pTNM-T, pTNM-N, stage, and patient survival (p>0.05). Conclusion: These results suggest that periostin might play a role during the biological progression of NSCLC, but may not be related to the clinical prognostic parameters.

참도박의 Wnt 경로 활성화를 통한 모발성장 효과 (Hair-growth Promoting Effect of Grateloupia elliptica Via the Activation of Wnt Pathway)

  • 강정일;김상철;전유진;고영상;유은숙;강희경
    • 생약학회지
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    • 제47권2호
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    • pp.143-149
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    • 2016
  • Grateloupia elliptica has been reported to have the proliferation effect of dermal papilla cells (DPCs), which play important roles in the regulation of hair cycle. In the present study, we examined in vitro and in vivo hair growth-promoting effect of Grateloupia elliptica. When isolated rat vibrissa follicles were treated with extract of G. elliptica, the hair-fiber lengths of the vibrissa follicles significantly increased. Furthermore, the G. elliptica extract accelerated the telogen-angen transition in C57BL/6 mice. To investigate the molecular mechanisms of the G. elliptica extract on the proliferation of DPCs, we examined the activation of $wnt/{\beta}$-catenin signaling which is known to regulate hair follicle development, differentiation and hair growth. The G. elliptica extract activated $wnt/{\beta}$-catenin signaling via the increase of ${\beta}$-catenin and phospho-$GSK3{\beta}$. In addition, the G. elliptica extract increased the level of cyclin E and CDK2, while the level of $p27^{kip1}$ was decreased. These results suggest that the the G. elliptica extract may induce hair growth by proliferation of DPCs via cell-cycle progression and the activation of $Wnt/{\beta}$-catenin signaling.

β-lapachone에 의한 A549 인체폐암세포의 apoptosis 유도와 cyclooxygenase-2 활성 저하 (β-Lapachone-Induced Apoptosis is Associated with Inhibition of Cyclooxygenase-2 Activity in Human Lung Cancer A549 Cells)

  • 최영현
    • 생명과학회지
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    • 제21권10호
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    • pp.1494-1499
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    • 2011
  • ${\beta}$-lapachone은 남미에 자생하는 lapacho 나무(Tabeuia avellanedae)의 수액에 함유된 quinone계열의 일종으로 많은 인체암세포에서 apoptosis를 유발하는 것으로 알려져 있다. 본 연구는 A549 인체폐암세포를 대상으로 ${\beta}$-lapachone에 의한 apoptosis 유발 과정에서 나타나는 또 다른 현상들을 조사하기 위하여 실시되었다. ${\beta}$-lapachone이 처리된 A549 세포는 처리 농도의 증가에 따라 생존율이 감소되었으며, 이는 apoptosis 유발과 연관이 있음을 MTT assay와 flow cytometry 분석을 통하여 확인하였다. ${\beta}$-lapachone에 의한 A549 세포의 증식억제는 종양억제유전자 p53과 cyclin-dependent kinase 저해제인 p21의 발현을 전사 및 번역 수준에서 증가시켰으며, p53 단백질의 인산화 증가와 연관성이 있었다. 또한 ${\beta}$-lapachone은 caspase-3과 -9를 활성화시켰으며, 활성화된 caspase-3의 기질 단백질들[poly(ADP-ribose) polymerase, ${\beta}$-catenin 및 phospholipase C-$\gamma$1]의 단편화를 유도하였다. 아울러 ${\beta}$-lapachone은 cyclooxygenase (COX)-2의 mRNA 및 단백질의 발현을 억제하였으나 COX-1의 발현에는 영향을 미치지 않았으며, ${\beta}$-lapachone에 의한 COX-2의 발현억제는 prostaglandin E2의 생성 저하에 관련이 있었다. 본 연구의 결과는 ${\beta}$-lapachone의 항암활성 기전의 이해와 더불어 ${\beta}$-lapachone이 폐암세포에서 강력한 항암활성이 있음을 보여 주는 것이다.

High Glucose Causes Human Cardiac Progenitor Cell Dysfunction by Promoting Mitochondrial Fission: Role of a GLUT1 Blocker

  • Choi, He Yun;Park, Ji Hye;Jang, Woong Bi;Ji, Seung Taek;Jung, Seok Yun;Kim, Da Yeon;Kang, Songhwa;Kim, Yeon Ju;Yun, Jisoo;Kim, Jae Ho;Baek, Sang Hong;Kwon, Sang-Mo
    • Biomolecules & Therapeutics
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    • 제24권4호
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    • pp.363-370
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    • 2016
  • Cardiovascular disease is the most common cause of death in diabetic patients. Hyperglycemia is the primary characteristic of diabetes and is associated with many complications. The role of hyperglycemia in the dysfunction of human cardiac progenitor cells that can regenerate damaged cardiac tissue has been investigated, but the exact mechanism underlying this association is not clear. Thus, we examined whether hyperglycemia could regulate mitochondrial dynamics and lead to cardiac progenitor cell dysfunction, and whether blocking glucose uptake could rescue this dysfunction. High glucose in cardiac progenitor cells results in reduced cell viability and decreased expression of cell cycle-related molecules, including CDK2 and cyclin E. A tube formation assay revealed that hyperglycemia led to a significant decrease in the tube-forming ability of cardiac progenitor cells. Fluorescent labeling of cardiac progenitor cell mitochondria revealed that hyperglycemia alters mitochondrial dynamics and increases expression of fission-related proteins, including Fis1 and Drp1. Moreover, we showed that specific blockage of GLUT1 improved cell viability, tube formation, and regulation of mitochondrial dynamics in cardiac progenitor cells. To our knowledge, this study is the first to demonstrate that high glucose leads to cardiac progenitor cell dysfunction through an increase in mitochondrial fission, and that a GLUT1 blocker can rescue cardiac progenitor cell dysfunction and downregulation of mitochondrial fission. Combined therapy with cardiac progenitor cells and a GLUT1 blocker may provide a novel strategy for cardiac progenitor cell therapy in cardiovascular disease patients with diabetes.

신경세포 분화에서 세포주기 조절인자로서의 NELL2 유전자의 역할 (NELL2 gene as regulator of cell cycle in neuron differentiation)

  • 정미림;오연미;박우생;박상규
    • Clinical and Experimental Pediatrics
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    • 제49권10호
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    • pp.1100-1105
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    • 2006
  • 목 적 : 신경세포 분화에 있어 NELL2가 세포 주기와 세포자 멸사에 어떤 영향을 미치는지를 규명하고자 하였다. 방 법 : HiB5 세포에 NELL2를 전달감염시켜 배양하여 세포수를 측정하였다. 세포자멸사를 분석하기 위해 DNA 분절검사를 시행하였으며 PI염색으로 DNA양을 측정하였다. 세포주기의 조절에 관여하는 단백질에 대한 NELL2의 효과를 측정하기 위하여 Western blot과 면역염색을 시행하였다. 결 과 : NELL2를 전달감염시킨 군에서 세포수가 의미가 있게 적었고 DNA 분절검사에서 세포자멸사를 확인하였으며 $G_1$ 정지가 증가하였다. Western blot과 면역염색결과 Rb단백, p53, E2F1(KH-95)이 NELL2를 전달감염시킨 군에서 증가하고 cyclin D가 NELL2를 전달감염시킨 군에서 감소하였다. 결 론 : HiB5 세포에서 NELL2에 의하여 일정 수준에서의 세포자멸사가 동반되고 세포 주기에 있어 $G_1$기의 정지가 일어나며 세포주기를 조절하는 단백질의 변화가 발생함을 확인하였다. 따라서 NELL2가 뇌에서 신경세포 분화에 중요한 역할을 할 걸로 생각된다.

Caspase-3 Specifically Cleaves $p21^{WAF1/CIP1}$ in the Earlier Stage of Apoptosis in SK-HEP-1 Human Hepatoma Cells

  • Park, Jeong-Ae;Kim, Kyu-Won;Kim, Shin-Il;Lee, Seung-Ki
    • 고려인삼학회:학술대회논문집
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    • 고려인삼학회 1998년도 Advances in Ginseng Research - Proceedings of the 7th International Symposium on Ginseng -
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    • pp.231-243
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    • 1998
  • In the present study, we provide evidence that ginsenoside $Rh_2$ (G-$Rh_2$) as well as staurosporine induces apoptosis of human hepatoma SK-HEP-1 cells by caspase 3-mediated processing of $p21^{WAFI/CIPI}$ in the early stage of apoptosls. Immunoblottings showed that G-$Rh_2$ as well as statrosporine induced the processing of caspase-3 to an active form, pl7. In stable Bcl-2 transfectants however, G-$Rh_2$ induced DNA fragmentation, while staurosporine did not. In the early stage of apoptosis, $p21^{WAFI/CIPI}$ was detected to undergo proteolytic processing specifically conducted by caspase-3. $p21^{WAFI/CIPI}$ translated in vitro was cleaved into a p14 fragment, when incubated with cell extracts obtained from either G-$Rh_2$- or staurosporine-treated cells. Cleavage was equally inhibited in both cases by adding Ac-DEVD-cho, a specific caspase-3 inhibitor, but not by Ac-YVkD-cho, a specific caspase-l inhibitor. Similarly, $p21^{WAFI/CIPI}$ was efficiently leaved by recombinant caspase-3 overexpressed in E. coli. Moreover, the endogenous $p21^{WAFI/CIPI}$ of untreated-cell extracts was also cleaved by recombinant caspase-3. Mutation analysis allowed identification of two caspase-3 cleavage sites, $DHVD^{112}$/L and $SMTD^{149}$/F, which are located within, or near the interaction domains for cyclins, Cdks, and PCNA. Taken together, these results show that G-$Rh_2$ as well as staurosporine increases caspase-3 activity, which in turn directly cleaves $p21^{WAFI/CIPI}$ resulting in elevation of Cdk kinase activity in the early stages of apoptosis. We propose that proteolytic cleavage of $p21^{WAFI/CIPI}$ is a functionally relevant event that allows unleashing the cyclin/Cdk activity from the inhibitor seen in the earlier stage of apoptosis, the event of which may be associated with the triggering mechanism for the execution of apoptosis.

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Apoptosis of Kinetin Riboside in Colorectal Cancer Cells Occurs by Promoting β-Catenin Degradation

  • TaeKyung Nam;Wonku Kang;Sangtaek Oh
    • Journal of Microbiology and Biotechnology
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    • 제33권9호
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    • pp.1206-1212
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    • 2023
  • The Wnt/β-catenin pathway plays essential roles in regulating various cellular behaviors, including proliferation, survival, and differentiation [1-3]. The intracellular β-catenin level, which is regulated by a proteasomal degradation pathway, is critical to Wnt/β-catenin pathway control [4]. Normally, casein kinase 1 (CK1) and glycogen synthase kinase-3β (GSK-3β), which form a complex with the scaffolding protein Axin and the tumor suppressor protein adenomatous polyposis coli (APC), phosphorylate β-catenin at Ser45, Thr41, Ser37, and Ser33 [5, 6]. Phosphorylated β-catenin is ubiquitinated by the β-transducin repeat-containing protein (β-TrCP), an F-box E3 ubiquitin ligase complex, and ubiquitinated β-catenin is degraded via a proteasome pathway [7, 8]. Colorectal cancer is a significant cause of cancer-related deaths worldwide. Abnormal up-regulation of the Wnt/β-catenin pathway is a major pathological event in intestinal epithelial cells during human colorectal cancer oncogenesis [9]. Genetic mutations in the APC gene are observed in familial adenomatous polyposis coli (FAP) and sporadic colorectal cancers [10]. In addition, mutations in the N-terminal phosphorylation motif of the β-catenin gene were found in patients with colorectal cancer [11]. These mutations cause β-catenin to accumulate in the nucleus, where it forms complexes with transcription factors of the T-cell factor/lymphocyte enhancer factor (TCF/LEF) family to stimulate the expression of β-catenin responsive genes, such as c-Myc and cyclin D1, which leads to colorectal tumorigenesis [12-14]. Therefore, downregulating β-catenin response transcription (CRT) is a potential strategy for preventing and treating colorectal cancer. Plant cytokinins are N6-substituted purine derivatives; they promote cell division in plants and regulate developmental pathways. Natural cytokinins are classified as isoprenoid (isopentenyladenine, zeatin, and dihydrozeatin), aromatic (benzyladenine, topolin, and methoxytopolin), or furfural (kinetin and kinetin riboside), depending on their structure [15, 16]. Kinetin riboside was identified in coconut water and is a naturally produced cytokinin that induces apoptosis and exhibits antiproliferative activity in several human cancer cell lines [17]. However, little attention has been paid to kinetin riboside's mode of action. In this study, we show that kinetin riboside exerts its cytotoxic activity against colon cancer cells by suppressing the Wnt/β-catenin pathway and promoting intracellular β-catenin degradation.

토마토와 라이코펜이 전립선암의 예방과 치료에 미치는 영향 (Effects of Tomatoes and Lycopene on Prostate Cancer Prevention and Treatment)

  • 황은선
    • 한국식품영양과학회지
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    • 제33권2호
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    • pp.455-462
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    • 2004
  • 토마토에는 라이코펜과 quercetin, phytoene, phytofluene, cyclolycopene, salicylates 그리고 tomatlne과 같은 다양한 생리활성 물질들이 함유되어 있으며, 이들은 라이코펜과 함께 항암작용에 관여하는 것으로 사료된다. 생리적 농도에서 라이코펜은 세포주기의 정지(arrest)와 세포 자가사멸을 통한 암세포의 생존률을 감소시키고, 사이클린을 조절하며, 세포간의 연락체계를 증가시키는 것으로 보고되고 있다. 라이코펜은 산화에 민감하여 매우 쉽게 산화물질을 만든다. 토마토 제품의 섭취는 혈중 phytoene, phytofluene 그리고 라이코펜 산화물질인 cyclolycopene의 농도를 유의적으로 증가시켰다. 또한 토마토나 토마토 제품을 통한 라이코펜의 섭취는 혈중 라이코펜의 농도를 최고 1.26 $\mu$M까지 증가시켰다. 다양한 암 부위 (cancer sites)를 통한 19건의 동물실험결과, 10건의 실험에서 라이코펜이 효과가 입증되었고, 7건의 실험에서는 통계적인 유의성이 밝혀지지 않았고, 2건의 전립선암 실험에서는 억제효과를 보이지 않았다. 임상실험에서 라이코펜 섭취와 토마토 제품섭취군 모두 백혈구와 전립선에서 의 DNA 산화물질을 감소시킴을 확인하였다. 라이코펜은 암화과정을 방해하는 생리활성 물질로 밝혀졌으나 phytoene, phytofluene 그리고 cyclolycopene의 역할에 관해서는 아직 밝혀져 있지 않다. 따라서 라이코펜과 토마토에 함유되어 있는 다른 식물성 화학성분들(phytochemicals) 간의 상호작용에 관해서는 좀 더 구체적이고 신뢰성 있는 연구가 필요하다.

Resveratrol에 의한 A549 인체 폐암세포의 증식억제 및 apoptosis 유발에 관한 연구 (Induction of Cdk inhibitor p21 and inhibition of cyclooxygenase-2 by resveratrol in human lung carcinoma A549 cells.)

  • 김영애;임선영;이숙희;박건영;이원호;최영현
    • 생명과학회지
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    • 제14권5호
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    • pp.800-808
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    • 2004
  • Resveratrol은 포도와 같은 식물에서 각종 감염균으로부터 자신의 몸을 보호하기 위하여 생성되는 물질인 phytoalexin의 일종으로 강력한 항산화작용, 암예방 효과 및 항암 작용을 포함한 각종 약리작용을 가진 것으로 보고되어져 오고 있다. 본 연구에서는 resveratrol의 항암작용 기전해석을 위하여 A549 인체폐암세포의 종식에 미치는 resverakol의 영향을 조사하였다. A549 세포의 생존율은 resveratrol의 처리시간 증가에 따라 강력하게 억제되었으며, 이는 암세포의 다양한 형태변형을 동반한 세포주기 C2/M arrest 및 염색질 응축 현상을 동반한 apoptosis 유발에 의한 것임을 알 수 있었다. Resveratrol 처리에 의한 apoptosis 유발은 Bcl-2의 발현변화 없이 Bcl-$X_L$의 발현 감소에 따른 상대적인 Bax의 발현 증가와 Sp-1, PCNA 및 $\beta$-catenin 등과 같은 단백질의 분해 현상과 연관성이 있었다 또한 resveratrol에 의한 A549세포 의 증식억제는 Cdk inhibitor p21의 발현 증가에 따른 Cdks 의 kinase 활성 저하 및 COX-2의 선택적 저해에 따른 PGE2 생성 저하와 관련이 있었다.