• 제목/요약/키워드: apoptotic cells

검색결과 2,157건 처리시간 0.026초

Stigmasterol isolated from marine microalgae Navicula incerta induces apoptosis in human hepatoma HepG2 cells

  • Kim, Young-Sang;Li, Xi-Feng;Kang, Kyong-Hwa;Ryu, BoMi;Kim, Se Kwon
    • BMB Reports
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    • 제47권8호
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    • pp.433-438
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    • 2014
  • Plant sterols have shown potent anti-proliferative effects and apoptosis induction against breast and prostate cancers. However, the effect of sterols against hepatic cancer has not been investigated. In the present study, we assessed whether the stigmasterol isolated from Navicula incerta possesses apoptosis inductive effect in hepatocarcimona (HepG2) cells. According to the results, Stigmasterol has up-regulated the expression of pro-apoptotic gene expressions (Bax, p53) while down-regulating the anti-apoptotic genes (Bcl-2). Probably via mitochondrial apoptosis signaling pathway. With the induction of apoptosis caspase-8, 9 were activated. The DNA damage and increase in apoptotic cell numbers were observed through Hoechst staining, annexin V staining and cell cycle analysis. According to these results, we can suggest that the stigmasterol shows potent apoptosis inductive effects and has the potential to be tested as an anti-cancer therapeutic against liver cancer.

단천환이 사람신경세포의 산화적 손상에 미치는 영향 (Effects of Danchun-hwan on Oxidative Damage of Human Neural Cell)

  • 한상혁;김명선;이지현;김도환;나영훈;조광호;박래길;문병순
    • 대한한의학회지
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    • 제21권4호
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    • pp.183-192
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    • 2000
  • Objectives : The present study was carried out to investigate the effects of Danchun-hwan(DCH) on the peroxynitrite-induced neural cell death in human neuroblastoma cell line, SH-SY5Y. Methods : The cultured cells were pretreated with DCH and exposed to 3-morpholinosydnonimine(SIN-1) that simultaneously generates NO and superoxide, thus possibly forming peroxynitrite. The cell damage was assessed by using MTT assay and crystal violet staining. Results : Exposure of the cells to SIN-1 for 24hr induced 75% apoptotic cell death, as evaluated by the occurrence of morphological nuclear changes characteristic of apoptosis using 4', 6-diamidino-2-phenylinole(DAPI). However, pretreatment of SH-SY5Y with the water extracts of DCH, inhibited the apoptotic cell death in a dose-dependent manner. DCH also inhibited SIN-1-induced apoptotic caspase 3-like protease activity in a dose-dependent manner. DCH recovered the depleted glutathione levels by SIN-1. Conclusions : Taken together, it is suggested that DCH protected human neuroblastoma cell line, SH-SY5Y, from the free radical injury mediated by peroxynitrite by a mechanism of elevating antioxidant, GSH.

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RKIP Downregulation Induces the HBx-Mediated Raf-1 Mitochondrial Translocation

  • Kim, Sun-Young;Park, Sung-Goo;Jung, Hye-Yun;Chi, Seung-Wook;Yu, Dae-Yeul;Lee, Sang-Chul;Bae, Kwang-Hee
    • Journal of Microbiology and Biotechnology
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    • 제21권5호
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    • pp.525-528
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    • 2011
  • The Raf-1 kinase inhibitory protein (RKIP) can regulate multiple key signaling pathways. Specifically, RKIP binds to Raf-1 kinase and inhibits the Ras-Raf-1-MEK1/2- ERK1/2 pathway. Additionally, Raf-1 has been shown to translocate to mitochondria and thereby protect cells from stress-mediated apoptosis. Recently, HBx was found to stimulate the mitochondrial translocation of Raf-1, contributing to the anti-apoptotic effect. We found that RKIP was downregulated during HBx-mediated hepatocarcinogenesis. In this study, we show that RKIP bound to Raf-1 and consequently inhibited the translocation of Raf-1 into mitochondria. This promoted the apoptosis of cells treated with apoptotic stimulus. Thus, the downregulation of RKIP increased the level of free Raf-1 and thereby elevated the mitochondrial translocation of Raf-1 during HBx-mediated hepatocarcinogenesis. The elevated Raf-1 mitochondrial translocation induced the increased anti-apoptotic effect and subsequently promoted HBx-mediated hepatocarcinogenesis.

siRNA Interference with a Proliferation-Inducing Ligand Gene in the Sgr-7901 Gastric Carcinoma Cell Line

  • Ni, Shao-Zhong;Cao, Hong-Yong;Chen, Zheng;Zhu, Yi;Xu, Ze-Kuan
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권4호
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    • pp.1511-1514
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    • 2012
  • Objective: The present study aimed to investigate the influence of siRNA interference with a proliferation-inducing ligand (APRIL) gene on gastric carcinoma sgr-7901 cell apoptosis. Correlations between APRIL silencing and tyrosine kinase (trka) expression were also explored. Methods: Two APRIL-silencing siRNA vectors were constructed, and transfected into human gastric carcinoma sgr-7901 cells, expression before and after transfection being detected using RT-PCR and western blot analyses. The expression of 15 trka genes was detected using RT-PCR and apoptotic rates of sgr-7901 were assessed by flow cytometry. Results: The expression levels of receptor trka genes were significantly decreased, and the apoptotic rate of sgr-7901 was significantly increased after transfection (P < 0.05). Conclusion: APRIL gene silencing can increase the apoptotic rate of gastric carcinoma cells, and inhibit the expression of receptor trka genes. There is a correlation between the signaling pathways of APRIL and trka.

목향에탄올추출물의 ROS-MAPKs 경로를 통한 세포사멸 유도 (Ethanol Extract of Saussurea lappa Root Induces Apoptosis through an ROS-MAPKs-Linked Cascade)

  • 김대성;이성진;이장천;우원홍;임규상;문연자
    • 약학회지
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    • 제56권3호
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    • pp.173-179
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    • 2012
  • Saussurea lappa (SL) and major compounds, sesquiterpene lactones, have been suggested to possess various biological effects, including anti-tumor, anti-ulcer, anti-inflammatory, anti-viral and cardiotonic activities. Therefore, the ethanol extract of Saussurea lappa root (ESL) is studied for the mechanism of its action in apoptotic pathway. ESL-treated cells manifested nuclear condensation, and fragmentation. ESL also triggered the mitochondrial apoptotic pathway, as indicated by a change in Bax/Bcl2 ratio and caspase-9/-3 activation. ESL induced p38 MAPK/JNK, p53, and ASK1 phosphorylation. ROS scavenger reversed ESL-induced apoptotic cell death via inhibition of caspase-3 and p38 MAPK/JNK phosphorylation. These results suggest that ESL induced apoptosis in HepG2 cells through the ROS-p38/JNK pathway.

유세포 분석기를 이용한 galectin-3에 의해 유도된 흉선세포의 apoptosis 분석 (Flow cytometric analysis of apoptosis in mouse thymocytes by galectin-3)

  • 김태중;우희종
    • 대한수의학회지
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    • 제39권6호
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    • pp.1112-1118
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    • 1999
  • Galectin-3 plays an important role in cell development, differentiation and cancer metastasis, including cell-cell/extracellular matrix (ECM) interactions and is supposed to have an effect of apoptosis on T-cells in thymic clonal selection. In this study, to know the effect of galectin-3 on thymocyte development, we used recombinant human galectin-3 (rHgal-3) from Escherichia coli, JM105, which was inserted with human gal-3 gene-transformed plasmid vector (prGal-3) to express human galectin-3. Expressed rHgal-3 was confirmed by western blot using the culture supernant of hybridoma (M3/38) producing monoclonal antibody to human galectin-3. Sepharose gel affinity chromatography was used to purify the expressed rHgal-3. Thymocytes and hepatocytes from 6-week-old male BALB/c mice were incubated with rHgal-3 and showed marked increase of apoptotic population on analysis using flow cytometry with 7-AAD in a dosedependent manner. However, rHgal-3 failed to induce apoptosis on hepatocytes. Interestingly, this apoptotic effect was not inhibited by lactose, a specific lectin domain inhibitor. From these results, we concluded that extrinsic -3 induces apoptosis on mouse thymocytes, and galectin-3 may have an apoptotic effect on T-cells in thymic clonal selection.

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사람 동맥 평활근 세포에 대한 Rosmarinic Acid의 항동맥경화 활성 (Anti-Atherosclerosis Activity of Rosmarinic Acid in Human Aortic Smooth Muscle Cells)

  • 정재하;윤현정;허준영;김재은;박선동
    • 동의생리병리학회지
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    • 제23권6호
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    • pp.1423-1430
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    • 2009
  • Rosmarinic acid frequently found as a secondary metabolite in herbs and medicinal plants, has exhibited antimicrobial, antiviral, antioxidative, and anti-inflammatory activities. The proliferation and migration of human aortic smooth muscle cells (HASMC) in response to activation by various stimuli plays a critical role in the initiation and development of atherosclerosis. This study was conducted to examine the effects of Rosmarinic acid on the proliferation and migration of HASMC. Rosmarinic acid suppressed the proliferation of HASMC via induction of the expression of apoptotic proteins including cleaved poly ADP-ribose polymerase (PARP), and caspase-3. Rosmarinic acid decreased anti-apoptotic Bcl-2 and increased pro-apoptotic Bax. Moreover, treatment of rosmarinic acid decreased the G1/S cycle regulation proteins (cyclin D1, cyclin E, CDK2, CDK4 and CDK6) and increased p21, p27 and p53. Rosmarinic acid also blocked HASMC migration via suppression of MMP-9 and MMP-2. Taken together, these results indicate that rosmarinic acid has the potential for use as an anti-atherosclerosis agent.

매실 분획물에 의한 인체 대장암세포 억제 효과 (Inhibitory Effects of Prunus mume Solvent Fractions on Human Colon Cancer Cells)

  • 김정호;조현동;원영선;허지안;김지영;김휘곤;한심희;문광덕;서권일
    • 생명과학회지
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    • 제29권11호
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    • pp.1227-1234
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    • 2019
  • 매실은 한국, 일본 및 중국 등지에서 섭취하여온 과실로서 유기산이 풍부하며, 다량의 무기질 및 폴리페놀 성분을 함유한 것으로 알려져 있다. 이러한 매실을 이용하여 예로부터 절임이나 청 등으로 가공하여 섭취할 뿐만 아니라 구토, 해독 및 해열에 효능이 있는 한약재로서 사용해왔다. 본 연구에서는 매실을 이용하여 분획물을 제조하고 각각의 인체 대장암세포에 대한 성장 억제효과를 확인하였으며, colony 형성능, 형태학적 관찰, apoptotic body 형성, 단백질 변화 및 환경호르몬에 대한 방어 효과를 평가하였다. 매실 분획물의 인체 대장암세포 HT-29에 대한 증식 억제효과는 매실 메탄올 분획물(maesil methanol fraction, MMF) 및 매실 부탄올 분획물(maesil, butanol fraction, MBF)이 가장 뛰어난 효능을 나타내었다. MMF 및 MBF의 처리에 따라 colony 형성능 또한 농도의존적으로 감소하는 것으로 나타났으며 형태학적 변화 또한 확인할 수 있었다. 핵의 형태학적 변화를 관찰한 결과 $125{\mu}g/ml$의 MMF 및 MBF 처리에 따라 apoptotic body의 형성 및 핵 응축을 관찰하였다. MMF 및 MBF의 처리에 따른 인체 대장암세포의 성장 억제효과가 apoptosis 와 관련이 있는지 단백질의 변화를 확인한 결과, pro-apoptotic 단백질은 Bax, caspase-3, PARP의 발현이 농도의존적으로 증가하는 경향을 나타내었으며, anti-apoptotic 단백질인 Bcl-2의 발현은 감소하는 경향을 나타냈다. 또한, 환경호르몬의 일종은 bisphenol A (BPA)에 의해 성장이 증식된 HT-29세포는 MMF의 처리에 따라 유의적인 성장억제 효과를 갖는 것을 확인할 수 있었다. 따라서 본 연구를 통해 얻은 결과는 매실 분획물을 이용한 기능성 식품 소재화에 대한 기초 자료로 활용될 수 있을 것으로 판단된다.

Induction of MicroRNA-9 Mediates Cytotoxicity of Curcumin Against SKOV3 Ovarian Cancer Cells

  • Zhao, Song-Feng;Zhang, Xiao;Zhang, Xiao-Jian;Shi, Xiu-Qin;Yu, Zu-Jiang;Kan, Quan-Cheng
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권8호
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    • pp.3363-3368
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    • 2014
  • Background: Curcumin, a phenolic compound extracted from the rhizomes of Curcuma longa, has shown cytotoxic effects against a variety of cancers. The aim of this study was to identify potential microRNA (miRNA) mediators of the anticancer effects of curcumin in ovarian cancer cells. Materials and Methods: SKOV3 ovarian cancer cells were treated with curcumin ($10-60{\mu}M$) and miR-9 expression, cell proliferation, and apoptosis were assessed. The effects of miR-9 depletion on curcumin-mediated growth suppression were also examined. Phosphorylation of Akt and forkhead box protein O1 (FOXO1) was measured in cells with miR-9 overexpression or curcumin treatment. Results: Curcumin caused a significant and dose-dependent increase of miR-9 expression in SKOV3 cells, while significantly impeding cell proliferation and stimulating apoptosis. Depletion of miR-9 significantly (p<0.05) attenuated the growth-suppressive effects of curcumin on SKOV3 cells, coupled with reduced percentages of apoptotic cells. In contrast, overexpression of miR-9 significantly enhanced the cleavage of caspase-3 and poly(ADP-ribose) polymerase and promoted apoptotic death in SKOV3 cells. Western blot analysis showed that both miR-9 overexpression and curcumin similarly caused a significant (p<0.05) decline in the phosphorylation of Akt and FOXO1, compared to untreated cells. Conclusions: The present study provided evidence that curcumin exerts its cytotoxic effects against SKOV3 ovarian cancer cells largely through upregulation of miR-9 and subsequent modulation of Akt/FOXO1 axis. Further studies are needed to identify direct targets of miR-9 that mediate the anticancer effects of curcumin in ovarian cancer cells.

Phytochemicals from Goniothalamus griffithii Induce Human Cancer Cell Apoptosis

  • Banjerdpongchai, Ratana;Khaw-on, Patompong;Pompimon, Wialrt
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권7호
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    • pp.3281-3287
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    • 2016
  • Bioactive compounds extracted from leaves and twigs of Goniothalamus griffithii include pinocembrin (PCN) and goniothalamin (GTN). The objectives of this study were to investigate the cytotoxic activities of PCN and GTN and their influence on molecular signaling for cell death in several human cancer cell lines compared to normal murine fibroblast NIH3T3 cells. GTN exhibited the most potent cytotoxicity against MCF-7 > HeLa > HepG2 > NIH3T3 cells with $IC_{50}$ values of 7.33, 14.8, 37.1 and $65.4{\mu}M$, respectively, whereas PCN was cytotoxic only to HepG2 cells with $IC_{50}$ values of ${\sim}80{\mu}M$. Apoptotic cell death was confirmed by staining the cells with annexin V-FITC and propidium iodide (PI) employing flow cytometry. Apoptosis was shown by externalization of phosphatidylserine in goniothalamin-treated MCF-7 cells in a dose response manner. Positive PI-stained cells with the typical morphology of apoptotic cells were increased dose-dependently. Furthermore, reduction of mitochondrial transmembrane potential was found in goniothalamin-treated MCF-7, HepG2 and HeLa cells. GTN treatment in MCF-7 increased caspase-3, -8 and -9 activities while GTN-induced HeLa cells showed an increase of both caspase-3 and -9 activities. But an increased caspase-8 activity was demonstrated in GTN- and PCN-treated MCF-7 and HepG2 cells, respectively. Taken together, GTN- and PCN-induced human cancer cell apoptosis was through different molecular mechanisms or signaling pathways, which might be due to different machineries in different types of cancer cells, as evidenced by the compound-modulated caspase activities in both intrinsic and/or extrinsic pathways.