• Title/Summary/Keyword: cell apoptosis

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Clostridium difficile Toxin A Upregulates Bak Expression through PGE2 Pathway in Human Colonocytes

  • Kim, Young Ha;Kim, Ho
    • Journal of Microbiology and Biotechnology
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    • 제29권10호
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    • pp.1675-1681
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    • 2019
  • Clostridium difficile toxin A is known to cause colonic epithelial cell apoptosis, which is considered the main causative event that triggers inflammatory responses in the colon, reflecting the concept that the essential role of epithelial cells in the colon is to form a physical barrier in the gut. We previously showed that toxin A-induced colonocyte apoptosis and subsequent inflammation were dependent on prostaglandin E2 ($PGE_2$) produced in response to toxin A stimulation. However, the molecular mechanism by which $PGE_2$ mediates cell apoptosis in toxin A-exposed colonocytes has remained unclear. Here, we sought to identify the signaling pathway involved in toxin A-induced, $PGE_2$-mediated colonocyte apoptosis. In non-transformed NCM460 human colonocytes, toxin A exposure strongly upregulated expression of Bak, which is known to form mitochondrial outer membrane pores, resulting in apoptosis. RT-PCR analyses revealed that this increase in Bak expression was attributable to toxin A-induced transcriptional upregulation. We also found that toxin A upregulation of Bak expression was dependent on $PGE_2$ production, and further showed that this effect was recapitulated by an Prostaglandin E2(PGE2) receptor-1 receptor agonist, but not by agonists of other EP receptors. Collectively, these results suggest that toxin A-induced cell apoptosis involves $PGE_2$-upregulation of Bak through the EP1 receptor.

Hydroxyzine Induces Cell Death in Triple-Negative Breast Cancer Cells via Mitochondrial Superoxide and Modulation of Jak2/STAT3 Signaling

  • Shakya, Rajina;Park, Gyu Hwan;Joo, Sang Hoon;Shim, Jung-Hyun;Choi, Joon-Seok
    • Biomolecules & Therapeutics
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    • 제30권6호
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    • pp.585-592
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    • 2022
  • Treatment of triple-negative breast cancer (TNBC) has been limited due to the lack of molecular targets. In this study, we evaluated the cytotoxicity of hydroxyzine, a histamine H1 receptor antagonist in human triple-negative breast cancer BT-20 and HCC-70 cells. Hydroxyzine inhibited the growth of cells in dose- and time-dependent manners. The annexin V/propidium iodide double staining assay showed that hydroxyzine induced apoptosis. The hydroxyzine-induced apoptosis was accompanied down-regulation of cyclins and CDKs, as well as the generation of reactive oxygen species (ROS) without cell cycle arrest. The effect of hydroxyzine on the induction of ROS and apoptosis on TNBC cells was prevented by pre-treatment with ROS scavengers, N-acetyl cysteine or Mito-TEMPO, a mitochondria-targeted antioxidant, indicating that an increase in the generation of ROS mediated the apoptosis induced by hydroxyzine. Western blot analysis showed that hydroxyzine-induced apoptosis was through down-regulation of the phosphorylation of JAK2 and STAT3 by hydroxyzine treatment. In addition, hydroxyzine induced the phosphorylation of JNK and p38 MAPK. Our results indicate that hydroxyzine induced apoptosis via mitochondrial superoxide generation and the suppression of JAK2/STAT3 signaling.

자하거(紫河車)가 자궁근종세포(子宮筋腫細胞)의 성장억제(成長抑制)와 세포자멸사(細胞自滅死)에 미치는 영향(影響) (Effects of Hominis Placenta on the Growth of Human Uterine Myoma Cells and Cell Apoptosis)

  • 위효선;이진무;이창훈;조정훈;장준복;이경섭
    • 대한한방부인과학회지
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    • 제21권2호
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    • pp.38-48
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    • 2008
  • Purpose: This study was conducted to investigate the effects of Hominis Placenta (紫河車) on the growth of human uterine myoma cells and cell apoptosis. Methods: Human uterine leiomyoma cells were cultured and treated with Hominis Placenta extract for 48 hours. Cell proliferation and activity was analyzed by MTT assay. We analyzed the cell cycle of human uterine myoma cells treated Hominis Placenta extract by FACS. Expression of proteins related to cell apoptosis (Bax, Bcl-2), cyclin-D1 and VEGF were evaluated by Western blotting method. Results: The human uterine myoma cells treated by Hominis Placenta extract didn't proliferate below the concentration of $10mg/m{\ell}$. And there was no remarkable difference on cell cycle analysis below the concentration of $10mg/m{\ell}$. The expression of Bax was decreased and the expression of Bcl-2 was increased after the treatment of Hominis Placenta extract. But the expressions of cyclin-D1 and VEGF were increased after the treatment of Hominis Placenta extract. Conclusion: This study suggests that Hominis Placenta induce uterine myoma cell apoptosis and have effect on the myoma cell proliferation in the concentraion below $10mg/m{\ell}$.

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Apoptotic effect of $IP_6$ was not enhanced by co-treatment with myo-inositol in prostate carcinoma PC3 cells

  • Kim, Hyun-Jung;Jang, Yu-Mi;Kim, Harriet;Kwon, Young-Hye
    • Nutrition Research and Practice
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    • 제1권3호
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    • pp.195-199
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    • 2007
  • Inositol hexaphosphate ($IP_6$) is a major constituent of most cereals, legumes, nuts, oil seeds and soybean. Previous studies reported the anticancer effect of $IP_6$ and suggested that co-treatment of $IP_6$ with inositol may enhance anticancer effect of $IP_6$. Although the anticancer effect of $IP_6$ has been intensively studied, the combinational effect of $IP_6$ and inositol and involved mechanisms are not well understood so far. In the present study, we investigated the effect of $IP_6$ and myo-inositol (MI) on cell cycle regulation and apoptosis using PC3 prostate cancer cell lines. When cell, were co-treated with $IP_6$ and MI, the extent of cell growth inhibition was significantly increased than that by $IP_6$ alone. To identify the effect of $IP_6$ and MI on apoptosis, the activity of caspase-3 was measured. The caspase-3 activity was significantly increased when cells were treated with either $IP_6$ alone or both $IP_6$ and MI, with no significant enhancement by co-treatment. To investigate the effect of $IP_6$ and MI of cell cycle arrest, we measured p21 mRNA expression in PC3 cells and observed significant increase in p21 mRNA by $IP_6$. But synergistic regulation by co-treatment with $IP_6$ and MI was not observed. In addition, there was no significant effect by co-treatment compared to $IP_6$ treatment on the regulation of cell cycle progression although $IP_6$ significantly changed cell cycle distribution in the presence of MI or not. Therefore, these findings support that $IP_6$ has anticancer function by induction of apoptosis and regulation of cell cycle. However, synergistic effect by MI on cell cycle regulation and apoptosis was not observed in PC3 prostate cancer cells.

혈부축어탕(血府逐瘀湯) 자궁근종세포의 증식억제와 Apoptosis 관련 유전자 발현에 미치는 영향 (Effect of Hyulbuchukeotang on the Inhibition of Proliferation of Uterine leiomyoma cells and Cell apoptosis)

  • 문나영;백승희;김동철
    • 대한한방부인과학회지
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    • 제19권2호
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    • pp.186-198
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    • 2006
  • Purpose : The purpose of this study is to demonstrate the direct inhibitory effect of Hyulbuchukeotang on the proliferation of uterine leiomyoma cells through an experiment treating uterine leiomyoma cells cultivated by explantation with indicated concentrations of Hyulbuchukeotang and to research the gene expression related to cell cycle ill order to discover the connection with apoptosis and its mechanism by analyzing cell cycle. Methods : After primary culture of uterine leiomyoma cells, the cultivated uterine leiomyoma cells were treated with indicated concentrations of Hyulbuchukeotang for 24 hours. The inhibitory effect on the cell proliferation was determined by the cell count assay. The value of a cell count assay represent the percentage of cells in a phase of the cell cycle compared with total cells. In addition, a link between Hyulbuchukeotang and apoptosis was examined through flow cytometric analysis by FACS and DNA fragmentation analysis. Finally, the degree of gene expression related to cell cycle was evaluated by Western blot analysis. Results : The inhibitory effect of Hyulbuchukeotang increase of uterine leiomyoma cells treated with indicated concentrations of Hyulbuchkeotang increases. The result of gene expression related to G1 phase after treating with 100, 250, 500, 1,000 ${\mu}g/ml$ concentrations of Hyulbuchukeotang. on uterine leiomyoma cells is that the gene expression of p27 was increased but that of p53 an p21 remained unchanged and the gene of pRB, pro-caspase 3 was decreased. Conclusion Through the mentioned experiments, it is demonstrated that Hyulbuchkeotang is effective in inhibiting Proliferation of uterine leiomyoma cells by extending cell cycle G1. However it is not considered that the inhibitory effect results from the aptoposis.

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실험동물에서 Apoptosis의 모델개발과 생체면역반응 및 형태학적 특징 I. Apoptosis 및 Hepatic Tumorigenesis의 유도 및 관련지표의 검색 (Development of Apoptosis Model and Bioimmune Responses in Experimental Animal I. Induction and Indicator of Apoptosis and Hepatic Tumorigenesis)

  • 강정부;하우송;김지경
    • 한국임상수의학회지
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    • 제16권1호
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    • pp.100-107
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    • 1999
  • Apoptosis is now widely recognized as a common form of cell death and represents mechanism of cell clearance in many physiological situations where deletion of cells is required. In vivo administration of bacterial lipopolysaccharide (LPS) to Balb/c mice induced DNA fragmentation in the thymus. DNA fragmentation in the thymus was roughly dependent on the dose of LPS injected and reached the peak 18 hours after injection. This apoptosis in the thymus might be mediated due to LPS stimulant. DEN (diethylnitrosamine) has been shown to cause liver cancer in experimental animals and humans. The hepatic tumorigenesis was induced by ad libitum feeding of DEN only. It was suggested that DEN induced hepatic tumorgenesis in rat is a good reproducible model for studying biochemical and pathophysiological changes associated with the development of hepatic tumorigenesis and apoptosis.

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췌장암 세포주 MIA PaCa-2에서 황백 물 추출물에 의한 Apoptosis 유도 및 작용기전 (Apoptotic Effect of Phellodendri Cortex Water Extract on MIA PaCa-2 Cells)

  • 이인영;정황산;원진희
    • 동의생리병리학회지
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    • 제27권2호
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    • pp.202-211
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    • 2013
  • The purpose of this study is to investigate the apoptotic effect of Phellodendri Cortex water extract (PCWE) on pancreatic cancer cells and to find out the regulating mechanisms. Human-derived pancreatic cancer cell line, MIA PaCa-2 cells were treated by PCWE with various concentrations and the cytotoxicity was determined by MTT assay. The activation of Annexin V, DNA fragmentation, cell cycle arrest and caspase activation were observed to investigate the role of PCWE in pancreatic cancer cells. Also, to find out the regulating mechanisms, we examined the ROS production. The treatment of PCWE induced the cell death in both concentration and time dependent manner. The treatment of PCWE also increased the expression of Annexin V, DNA fragmentation, cell cycle arrest, and cleavage of caspase, which means cell-death PCWE induced was apoptosis but not necrosis. The ROS production was increased by PCWE treatment and the blockade of ROS inhibited the PCWE-induced cell death. These results could suggest that PCWE induced apoptosis via ROS release in pancreatic cancer cell.

Can Cancer Therapy be Achieved by Bridging Apoptosis and Autophagy: a Method Based on microRNA-Dependent Gene Therapy and Phytochemical Targets

  • Vijayarathna, Soundararajan;Gothai, Sivapragasam;Jothy, Subramanion L;Chen, Yeng;Kanwar, Jagat R;Sasidharan, Sreenivasan
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권17호
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    • pp.7435-7439
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    • 2015
  • A failure of a cell to self destruct has long been associated with cancer progression and development. The fact that tumour cells may not instigate cell arrest or activate cell death mechanisms upon cancer drug delivery is a major concern. Autophagy is a mechanism whereby cell material can be engulfed and digested while apoptosis is a self-killing mechanism, both capable of hindering multiplication after cell injury. In particular situations, autophagy and apoptosis seem to co-exist simultaneously or interdependently with the aid of mutual proteins. This review covers roles of microRNAs and chemopreventive agents and makes an attempt at outlining possible partnerships in maximizing cancer cell death with minimal normal cell damage.

Combined Effects of Curcumin and Triptolide on an Ovarian Cancer Cell Line

  • Cai, Ying-Ying;Lin, Wei-Ping;Li, Ai-Ping;Xu, Jian-Yang
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권7호
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    • pp.4267-4271
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    • 2013
  • Background: As natural medicines in Asia, curcumin and triptolide extracted from different drug plants have proven to possess anticancer potential and widely used for anti-cancer research. The present study attempted to clarify that curcumin and triptolide synergistically suppress ovarian cancer cell growth in vitro. Methods: To test synergic effects, cell viability and apoptosis were analyzed after curcumin and triptolide combination treatment on ovarian cancer cell lines. Synergistic effects on apoptosis induction were determined by lactate dehydrogenase (LDH) leakage assay, intracellular reactive oxygen species (ROS) assay, mitochondrial membrane potential (MMP) loss assay and flow cytometry analysis. Critical regulators of cell proliferation and apoptosis related were analyzed by qRT-PCR and Western blotting. Results: We showed that the combination of curcumin and triptolide could synergistically inhibit ovarian cancer cell growth, and induce apoptosis, which is accompanied by HSP27 and HSP70, indicating that HSP27 and HSP70 play the important role in the synergic effect. Conclusions: From the result present here, curcumin and triptolide combination with lower concentration have a synergistic anti-tumor effect on ovarian cancer and which will have a good potential in clinical applications.

2-Chloroethylethyl Sulfide Induces Apoptosis and Necrosis in Thymocytes

  • Hur, Gyeung-Haeng;Kim, Yun-Bae;Shin, Sung-Ho
    • BMB Reports
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    • 제31권2호
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    • pp.183-188
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    • 1998
  • 2-chloroethylethyl sulfide (CEES) is an alkylating agent that readily reacts with a wide variety of biological molecules causing metabolic abnormality. The mechanism of cell death during CEES injury is poorly understood. We have examined the effect of exposure of thymocytes with various concentrations of CEES to determine the pattern of cell death in thymocytes injury induced by CEES. In the present study, we show that two patterns of cell death occurred by either one of two mechanisms: apoptosis and necrosis. Exposure to low level of CEES (100 ${\mu}M$) for 5 h caused an induction of apoptosis on thymocytes, as identified by the following criteria: DNA fragmentation visualized by the characteristic "ladder" pattern was observed upon agarose gel electrophoresis and morphological features were revealed by microscopical observations. In contrast, exposure to high levels of CEES (500 ${\mu}M$) induce necrotic features such as cell lysis. Thus, depending on the concentrations, CEES can result in either apoptotic or necrotic cell damage. Our findings suggest that thymocytes which are not killed directly, but merely injured by low levels of CEES, are able to activate an internally-programmed cell death mechanism, whereas thymocytes receiving severe damages apparently can not.

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