• Title, Summary, Keyword: cell apoptosis

Search Result 3,742, Processing Time 0.069 seconds

NF-${\kappa}B$ Inhibitor Suppresses Hypoxia-induced Apoptosis of Mouse Pancreatic ${\beta}$-cell Line MIN6

  • Koh, Hyun Sook;Kim, Jae Young
    • Biomedical Science Letters
    • /
    • v.20 no.1
    • /
    • pp.14-24
    • /
    • 2014
  • Hypoxia is one of the main reasons for islet apoptosis after transplantation as well as during isolation. In this study, we attempted to determine the potential usefulness of NF-${\kappa}B$ inhibitor for suppression of hypoxia-induced ${\beta}$-cell apoptosis as well as the relationship between IP-10 induction and ${\beta}$-cell apoptosis in hypoxia. To accomplish this, we cultured the mouse pancreatic ${\beta}$-cell line MIN6 in hypoxia (1% $O_2$). Among several examined chemokines, only IP-10 mRNA expression was induced under hypoxia, and this induced IP-10 expression was due to NF-${\kappa}B$ activity. Since a previous study suggested that IP-10 mediates ${\beta}$-cell apoptosis, we measured hypoxia-induced IP-10 protein and examined the effect of anti-IP-10 neutralizing Ab on hypoxia-induced ${\beta}$-cell apoptosis. However, IP-10 protein was not detected, and anti-IP-10 neutralizing Ab did not rescue hypoxia-induced MIN6 apoptosis, indicating that there is no relationship between hypoxia-induced IP-10 mRNA expression and hypoxia-induced ${\beta}$-cell apoptosis. Since it was still not clear if NF-${\kappa}B$ functions as an apoptotic or anti-apoptotic mediator in hypoxia-induced ${\beta}$-cell apoptosis, we examined possible involvement of NF-${\kappa}B$ in hypoxia-induced ${\beta}$-cell apoptosis. Treatment with 1 ${\mu}M$ NF-${\kappa}B$ inhibitor suppressed hypoxiainduced apoptosis by more than 50%, while 10 ${\mu}M$ AP-1 or 4 ${\mu}M$ NF-AT inhibitor did not, indicating involvement of NF-${\kappa}B$ in hypoxia-induced ${\beta}$-cell apoptosis. Overall, these results suggest that IP-10 is not involved in hypoxia-induced ${\beta}$-cell apoptosis, and that NF-${\kappa}B$ inhibitor can be useful for ameliorating hypoxia-induced ${\beta}$-cell apoptosis.

Dihydroartemisinine Enhances Dictamnine-induced Apoptosis via a Caspase Dependent Pathway in Human Lung Adenocarcinoma A549 Cells

  • An, Fu-Fei;Liu, Yuan-Chong;Zhang, Wei-Wei;Liang, Lei
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.14 no.10
    • /
    • pp.5895-5900
    • /
    • 2013
  • Dictamnine (Dic) has the ability to exert cytotoxicity in human cervix, colon, and oral carcinoma cells and dihydroartemisinin (DHA) also has potent anticancer activity on various tumour cell lines. This report explores the molecular mechanisms by which Dic treatment and combination treatment with DHA and Dic cause apoptosis in human lung adenocarcinoma A549 cells. Dic treatment induced concentration- and time-dependent cell death. FCM analysis showed that Dic induced S phase cell cycle arrest at low concentration and cell apoptosis at high concentration in which loss of mitochondrial membrane potential (${\Delta}{\Psi}m$) was not involved. In addition, inhibition of caspase-3 using the specific inhibitor, z-DQMD-fmk, did not attenuate Dic-induced apoptosis, implying that Dic-induced caspase-3-independent apoptosis. Combination treatment with DHA and Dic dramatically increased the apoptotic cell death compared to Dic alone. Interestingly, pretreatment with z-DQMD-fmk significantly attenuated DHA and Dic co-induced apoptosis, implying that caspase-3 plays an important role in Dic and DHA co-induced cell apoptosis. Collectively, we found that Dic induced S phase cell cycle arrest at low concentration and cell apoptosis at high concentration in which mitochondria and caspase were not involved and DHA enhanced Dic induced A549 cell apoptosis via a caspase-dependent pathway.

Cysteine Participates in Cell Proliferation by Inhibiting Caspase3-like Death Protease

  • Lee, Sang-Han;Hong, Soon-Duck
    • Journal of Life Science
    • /
    • v.9 no.1
    • /
    • pp.9-13
    • /
    • 1999
  • Reduced thiols were important compounds for the maintenance of leukemia and lymphoma cell survival (and growth). In the course of examining the microenvirn-mental effects on lymphoma and leukemia cell growth, we found that cysteine suppressed apoptosis in these cells. In a present study, in order to investigate the role of cystein on the suppression of apoptotic cell death, we used CS21, P388, and L1210 cell lines. The addition of BSO, an inhibitor of glutathione synthase, induced apoptosis of these cells by blocking the cellular uptake of cysteine in CS21 cells. Although L1210 cells underwent apoptosis without thiol compounds, the addition of these compounds suppressed the apoptosis and promoted the growth or L1210 cells. When specific inhibitors of caspase3-like proteases, but not caspase1-like proteases, were activated during the L1210 cell apoptosis but the addition of thiol compounds suppressed the activation of caspase3-like proteases. These results suggest that reduced thiols including cysteine play an important role in the suppression of cell apoptosis by inhibiting the activation of caspase3-like proteases.

  • PDF

The Protective Effects of N-Acetyl-L-cysteine on Cadmium-induced Cell Apoptosis in Rat Testis

  • Kim, Ji-Sun;Soh, Jaemog
    • Biomedical Science Letters
    • /
    • v.25 no.4
    • /
    • pp.417-425
    • /
    • 2019
  • Cadmium (Cd) generates reactive oxygen species (ROS), which in turn cause the apoptosis of various cell types including developing germ cells in rodent testis. Ascorbic acids (AA), one of the ROS scavengers, had been reported to protect against Cd-induced apoptosis. N-Acetyl-L-cysteine (NAC), another ROS scavenger, is known to remove ROS and alleviate the Cd-induced apoptosis in various cell types. In this study we tried to elucidate how NAC affected on Cd-induced cell apoptosis in rat testis. Rats were administered with NAC before and after Cd treatment and then testicular cell apoptosis was examined. NAC treatment resulted in the reduction of Cd-induced chromosomal DNA fragmentation in agarose gel electrophoresis. Terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assay showed that treatment of NAC reduced the Cd-induced apoptosis of germ cells. The administration of NAC showed that the translocation of apoptosis inducing factor (AIF) from mitochondria to nucleus was prevented, which indicated that the mechanism of Cd-induced testicular apoptosis is mediated through the release of AIF in caspase-independent manner. Taken together, the NAC may remove Cd-induced ROS and protect ROS-induced cell apoptosis in rat testis.

Inhibitory Effects of Phenolic Alkaloids of Menispermum Dauricum on Gastric Cancer in Vivo

  • Zhang, Hong-Feng;Wu, Di;Du, Jian-Kuo;Zhang, Yan;Su, Yun-Ming
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.15 no.24
    • /
    • pp.10825-10830
    • /
    • 2015
  • The present study was conducted to investigate effects and mechanisms of action of phenolic alkaloids of Menispermum dauricum (PAMD) on gastric cancer in vivo. In vitro, cell apoptosis of human gastric cancer cell line SGC-7901 was observed using fluorescence staining. In vivo, a mice model was constructed to observe tumor growth with different doses. Cell apoptosis was examined using flow cytometry and K-RAS protein expression using Western blotting. The mRNA expression of P53, BCL-2, BAX, CASPASE-3, K-RAS was examined by real-time PCR. PAMD significantly suppressed tumor growth in the xenograft model of gastric cancer in a dose-dependent manner (p<0.01). Functionally, PAMD promoted cell apoptosis of the SGC-7901 cells and significantly increased the rate of cell apoptosis of gastric tumor cells (p<0.05). Mechanically, PAMD inhibited the expression of oncogenic K-RAS both at the mRNA and protein levels. In addition, PAMD affected the mRNA expression of the cell apoptosis-related genes (P53, BCL-2, BAX, CASPASE-3). PAMD could suppress gastric tumor growth in vivo, possibly through inhibiting oncogenic K-RAS, and induce cell apoptosis possibly by targeting the cell apoptosis-related genes of P53, BCL-2, BAX, CASPASE-3.

Nuclear Factor-κB Activation: A Question of Life or Death

  • Shishodia, Shishir;Aggarwal, Bharat B.
    • BMB Reports
    • /
    • v.35 no.1
    • /
    • pp.28-40
    • /
    • 2002
  • Apoptosis is a mode of cell death that plays an important role in both pathological and physiological processes. Research during the last decade has delineated the entire machinery needed for cell death, and its constituents were found to pre-exist in cells. The apoptotic cascade is triggered when cells are exposed to an apoptotic stimulus. It has been known for several years that inhibitors of protein synthesis can potentiate apoptosis that is induced by cytokines and other inducers. Until 1996, it was not understood why protein synthesis inhibitors potentiate apoptosis. Then three reports appeared that suggested the role of the transcription factor NF-${\kappa}B$ activation in protecting the cells from TNF-induced apoptosis. Since then several proteins have been identified that are regulated by NF-${\kappa}B$ and are involved in cell survival, proliferation, and protection from apoptosis. It now seems that when a cell is attacked by an apoptotic stimulus, the cell responds first by activating anti-apoptotic mechanisms, which mayor may not be followed by apoptosis. Whether or not a cell undergoes proliferation, the survival, or apoptosis, appears to involve a balance between the two mechanisms. Inhibitors of protein synthesis seem to suppress the appearance of protein that are involved in anti-apoptosis. The present review discusses how NF-${\kappa}B$ controls apoptosis.

Toosendan Fructus Induces Apoptotic Cell Death in MCF-7 Cell, Via the Inhibition of Bcl-2 Expression (천련자 메탄올 추출물이 Bcl-2 발현 억제를 통해 유방암 세포의 자멸사에 미치는 영향)

  • Yoon, Woo-Kyeong;Kim, Dong-Chul
    • The Journal of Korean Obstetrics and Gynecology
    • /
    • v.21 no.3
    • /
    • pp.18-33
    • /
    • 2008
  • Purpose: The research is to investigate the effect of TFE on apoptosis of human-derived breast cancer cells, to find out the relationship with apoptosis. Methods: Human-derived breast adenocarcinoma cell line, MCF-7 cells were treated by TFE with various concentration. The inducement effect of TFE on cell apoptosis was observed with MTT assay and the relationship between the treatment and apoptosis was investigated with FACS analysis, TUNEL assay and DNA laddering assay and the change in the protein levels of PARP and caspase-3 activities were also observed. The release of cytochrome-c was observed to find out the pathway of apoptosis induced by TFE. Results: The cell apoptosis was significantly induced in MCF-7 cells treated with TFE in concentration-dependent and time-dependent manner. It was verified by FACS analysis, TUNEL assay, DNA laddering assay that cell-death was caused not by necrosis but by apoptosis. The activity of PARP and caspase were increased concentration-dependently. The release of cytocrome-c was decreased in proportion to the concentration of the fruit extract. It therefore demonstrated that mitochondria were involved in apoptosis induced by TFE. The appearance of Bcl-2 protein was decreased concentration-dependently. Conclusion: The treatment by TFE induced apoptosis of human breast adenocarcinoma cell line, MCF-7. It seems likely that cell-death was caused by apoptosis and mitochondria were involved in it. The mechanism of protein change causing apoptosis seems related to the inhibition of Bcl-2 protein, the promotion of inversion from cytochrome-c into cytosol, the activation of caspase and the promotion of PARP cleavage.

  • PDF

Effects of Acanthopanacis Cortex Radicis on the Apoptosis in HeLa cell and MCF-7 cell (HeLa cell과 MCF-7 cell에 대한 오가피(五加皮)의 apoptosis 효과)

  • Kim, Kyung-Sook;Lee, Jin-Moo;Lee, Chang-Hoon;Jang, Jun-Bock;Lee, Kyung-Sub
    • The Journal of Korean Obstetrics and Gynecology
    • /
    • v.24 no.3
    • /
    • pp.14-27
    • /
    • 2011
  • Objectives: This study was designed to investigate the effects of Acanthopanacis Cortex Radicis extract(ACRE) on the apoptosis in HeLa cell and MCF-7 cell. Methods: After treatment with various concentration of ACRE, cell growth was evaluated in HeLa cell and MCF-7 cell. Hoechst 33342 staining was performed to estimate DNA fragment effect of ACRE on the apoptosis in HeLa cell and MCF-7 cell. Annexin V/PI apoptosis assay was used to estimate the effects of ACRE on the early apoptosis in HeLa cell and MCF-7 cell. RT-PCR was used to estimate the apoptosis gene expression effect of ACRE on Hela cell MCF-7 cell. Results: Under $0.1mg/m\ell$ of ACRE, cytotoxic effect was not found per NIH3T3 cell. The viability of HeLa cell and MCF-7 cells was significantly decreased ACRE ($100{\mu}g/m\ell$) in HeLa cell and MCF-7 cell, ACRE ($50{\mu}g/m\ell$) in HeLa cell 3 days after treatment, in MCF-7 cell 1&3 days after treatment (p<0.01). DNA fragmentation was observed 3 days after treatment of cl of ACRE on HeLa cell and MCF-7 cell. In Annexin V/PI apoptosis assay, after treatment of $100{\mu}g/m\ell$ of ACRE, the early apoptotic cell increased both in HeLa cell and MCF-7 cell. In RT-PCR analysis, after treatment of $100{\mu}g/m\ell$ of ACRE, bcl-2 were decreased and bax, caspase-3 were increased both in HeLa cell and MCF-7 cell. Conclusions: ACRE appears to have considerable activity on the apoptosis in HeLa cell and MCF-7 cell.

Induction of Apoptosis by Ginsenoside Rc on SK-MEL-28 Cell Lines (인체 흑색종세포에서 Ginsenoside Rc에 의한 Apoptosis의 유도)

  • Choi Su La;Myung Pyung Keun;Jeong Seung Il;Chun Hyun Ja;Baek Seung Hwa
    • Journal of Physiology & Pathology in Korean Medicine
    • /
    • v.17 no.1
    • /
    • pp.209-212
    • /
    • 2003
  • A wide variety of cancer chemotherapeutic agents have been shown to induce programmed cell death (PCD, apoptosis) in various tumor cell fines in vitro. This study was performed to know how ginsenoside Rc affect on SK-MEL-28 cell line, and how they induce the apoptosis. SK-MEL-28 cell lines were treated with various concentrations of ginsenoside Rc and cultured for various times. At cell cycle analysis, cells arrested at G2/M phase by ginsenoside Rc and apotosis percentage increased along with increasing concentration and time. TUNEL assay was performed to know whether SK-MEL-28 cell fine die as apoptosis or necrosis by ginsenoside Rc. As a result, fluorescence increased along with increasing time and concentration. Fas expressed on SK-MEL-28 cell lines membrane by ginsenoside Rc was identified using flow cytometer. Ginsenoside Rc induced apoptosis against SK-MEL-28 cell fines, and the apoptosis mechanism was identified as Fas-mediated apotosis.

Regulation of Caspase Activity During Apoptosis Induced by Baicalein in HL60 Human Leukemia Cell Line

  • Byun, Boo-Hyeong;Kim, Bu-Yeo
    • Food Science and Biotechnology
    • /
    • v.17 no.6
    • /
    • pp.1305-1309
    • /
    • 2008
  • Baicalein, one of the major flavonoid in Scutellaria baicalensis, has been known for its effects on proliferation and apoptosis of many tumor cell lines. Most biological effects of baicalein are thought to be from its antioxidant and prooxidant activities. In this report, baicalein was found to induce apoptosis in HL60 human promyelocytic leukemia cell line. Baicalein treatment induced DNA fragmentation and typical morphological features of apoptosis. To elucidate the mechanism of baicalein-induced apoptosis, the activities of the members of caspase family were measured. Interestingly caspase 2, 3, and 6 were significantly activated whereas caspase 1, 8, and 9 were not activated, suggesting selective involvement of specific caspases. Further, treatment with caspase inhibitors also supports the involvement of caspase 2 in apoptosis process. Although it has been reported that baicalein can induce apoptosis through many caspase pathways, the present study indicates that caspase 2 not caspase 9 pathway may be the important step in apoptosis on HL60 cell line.