• BMB Reports
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• v.41 no.1
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• pp.1-10
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• 2008

Surgery, Chung-Ang Unviersity College of Medicine, Yong-San Hospital, Seoul, Korea Apoptosis is considered to be a programmed and controlled mode of cell death, whereas necrosis has long been described as uncontrolled and accidental cell death resulting from extremely harsh conditions. In the following review, we will discuss the features and physiological meanings as well as recent advances in the elucidation of the signaling pathways of both apoptotic cell death and programmed necrotic cell death.

• Journal of Microbiology and Biotechnology
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• v.33 no.8
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• pp.992-997
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• 2023

Ferroptosis is a new kind of programmed cell death of which occurrence in microorganisms is not clearly verified. The elevated level of reactive oxygen species (ROS) influences cellular metabolisms through highly reactive hydroxyl radical formation under the iron-dependent Fenton reaction. Iron contributes to ROS production and acts as a cofactor for lipoxygenase to catalyze poly unsaturated fatty acid (PUFA) oxidation, exerting oxidative damage in cells. While ferroptosis is known to take place only in mammalian cells, recent studies discovered the possible ferroptosis-like death in few specific microorganisms. Capacity of integrating PUFA into intracellular membrane phospholipid has been considered as a key factor in bacterial or fungal ferroptosis-like death. Vibrio species in bacteria and Saccharomyces cerevisiae in fungi exhibited certain characteristics. Therefore, this review focus on introducing the occurrence of ferroptosis-like death in microorganisms and investigating the mode of action underlying the cells based on contribution of lipid peroxidation and iron-dependent reaction.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.1
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• pp.63-68
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• 2005

Hydrogen peroxide ($H_2O_2$) causes oxidative stress and is considered as an inducer of cell death in various tissues. Two-pore domain $K^+$ ($K_{2p}$) channels may mediate $K^+$ efflux during apoptotic volume decreases (AVD) in zygotes and in mouse embryos. In the present study, we sought to elucidate linkage between $K_{2p}$ channels and cell death by $H_2O_2$. Thus $K_{2p}$ channels (TASK-1, TASK-3, TREK-1, TREK-2) were stably transfected in HEK-293 cells, and cytotoxicity assay was preformed using cell counting kit-8 (CCK-8). Cell survival rates were calculated using the cytotoxicity assay data and dose-response curve was fitted to the $H_2O_2$ concentration. Ionic currents were recorded in cell-attached mode. The bath solution was the normal Ringer solution and the pipette solution was high $K^+$ solution. In HEK-293 cells expressing TREK-1, TREK-2, TASK-3, $H_2O_2$ induced cell death did not change in comparison to non-transfected HEK-293. In HEK-293 cells expressing TASK-1, however, dose-response curve was significantly shifted to the left. It means that $H_2O_2$ induced cell death was increased. In cell attached-mode recording, application of $H_2O_2$ (300μM) increased activity of all $K_{2p}$ channels. However, a low concentration of $H_2O_2$ ($50{\mu}M$) increased only TASK-1 channel activity. These results indicate that TASK-1 might participate in $K^+$ efflux by $H_2O_2$ at low concentration, thereby inducing AVD.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.6
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• pp.509-516
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• 2014

Radiation therapy for variety of human solid tumors utilizes mechanism of cell death after DNA damage caused by radiation. In response to DNA damage, cytochrome c was released from mitochondria by activation of pro-apoptotic Bcl-2 family proteins, and then elicits massive $Ca^{2+}$ release from the ER that lead to cell death. It was also suggested that irradiation may cause the deregulation of $Ca^{2+}$ homeostasis and trigger programmed cell death and regulate death specific enzymes. Thus, in this study, we investigated how cellular $Ca^{2+}$ metabolism in RKO cells, in comparison to radiation-resistant A549 cells, was altered by gamma (${\gamma}$)-irradiation. In irradiated RKO cells, $Ca^{2+}$ influx via activation of NCX reverse mode was enhanced and a decline of $[Ca^{2+}]_i$ via forward mode was accelerated. The amount of $Ca^{2+}$ released from the ER in RKO cells by the activation of $IP_3$ receptor was also enhanced by irradiation. An increase in $[Ca^{2+}]_i$ via SOCI was enhanced in irradiated RKO cells, while that in A549 cells was depressed. These results suggest that ${\gamma}$-irradiation elicits enhancement of cellular $Ca^{2+}$ metabolism in radiation-sensitive RKO cells yielding programmed cell death.

• BMB Reports
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• v.35 no.1
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• pp.28-40
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• 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.

• International Journal of Oral Biology
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• v.31 no.1
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• pp.15-20
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• 2006

Concerns remain regarding the biocompatibility and adverse effects of dental casting alloys. The aim of this study was to understand the cytopathogenic effect of metal ions, which might be released from dental alloys, on oral squamous carcinoma(OSC) cells. The cellular morphology, viability, the type of cell death and molecular change in response to metal ion salt solutions including aluminum(Al), cobalt(Co), copper(Cu) and nickel(Ni) were examined. The $TC_{50}$ values for the metal ions with the exception of AI were estimated to be between 400 and $600{\mu}M$. The cells treated with the metal ions showed apoptotic change with the exception of Al ions. Metal ion-induced apoptosis was further confirmed using flow cytometric analysis. This study showed that the cytotoxicity and the mode of cell death by metal ions clearly depend on the cell type, the type of metal ion and the duration of exposure. The protein level of Rb, a tumor suppressor that affects apoptosis para-doxically, was higher in the cells treated with Co, Cu and Ni. It is believed that apoptosis and cell damage in the OSC cells treated with Co, Cu or Ni can be evoked by the regulation of Rb.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8419-8423
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• 2016

Purpose: Anti-cancer activity evaluation of aqueous extract of CRUEL (herbomineral formulation) capsules on renal cell carcinoma cell lines, and exploration of mechanisms of cell death. Materials and Methods: To detect the cytotoxic dose concentration in renal cell carcinoma (RCC) cells, MTT assays were performed and morphological changes after treatment were observed by inverted microscopy. Drug effects against RCC cell lines were assessed with reference to cell cycle distribution (flow cytometry), anti-metastatic potential (wound healing assay) and autophagy(RT-PCR). Results: CRUEL showed anti-proliferative effects against RCC tumor cell lines with an IC50 value of ${\approx}4mg/mL$ in vitro., while inducing cell cycle arrest at S-phase of cell cycle and inhibiting wound healing. LC3 was found to be up-regulated after drug treatment in RT-PCR resulting in an autophagy mode of cell death. Conclusions: This study provides the experimental validation for antitumor activity of CRUEL.

• Biotechnology and Bioprocess Engineering:BBE
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• v.10 no.6
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• pp.564-570
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• 2005

In the present study, the protective effects of Bcl-2 over-expression in a suspension culture (without any adaptation) and spent medium (low nutrient and high toxic metabolite conditions) were investigated. In the suspension culture without prior adaptation, the viability of the control cell line fall to 0% by day 7, whereas the Bcl-2 cell line had a viability of 65%. The difference in the viability and viable cell density between the Bcl-2 and control cell lines was more apparent in the suspension culture than the static culture, and became even more apparent on day 6. Fluorescence microscopic counting revealed that the major mechanism of cell death in the control cell line in both the static and suspension cultures was apoptosis. For the Bcl-2 cell lines, necrosis was the major mode of cell death in the static culture, but apoptosis became equally important in the suspension culture. When the NS0 6A1 cell line was cultured in spent medium taken from a 14 day batch culture, the control cell line almost completely lost its viability by day 5, whereas, the Bcl-2 still had a viability of 73%. The viable cell density and viability of the Bcl-2 cell line cultivated in fresh medium were 2.2 and 2.7 fold higher, respectively, than those of the control cultures. However, the viable cell density and viability of the Bcl-2 cultivated in the spent medium were 8.7 and 7.8 fold higher, respectively, than those of the control cultures. Most of the dead cells in the control cell line were apoptotic; whereas, the major cell death mechanisms in the Bcl-2 cell line were necrotic.

• Preventive Nutrition and Food Science
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• v.1 no.2
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• pp.269-277
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• 1996

Bacteriocins are proteins produced by a heterogeneous group of bacteria that have a bactericidal effect on closely related organisms. Recently, bacteriocins from lactic acid bacteria and other food-related organisms have been the subject of much research because of their potential as food biopreservatives. Various modifications of agar plate diffusion assays are the most widely used methods even though the limitations of such assays are generally recognized. The ability to obtain a concentrated crude preparation on bacteriocin by optimizing production parameters greatly simplifies recovery of bacteriocin on subsequent purification steps. Some studies performed to optimize bacteriocins have been purified to homogeneity, and the amino acid sequences of many of these purified bacteriocins have been determined. Obtaining characterization data on purified bacteriocin will minimize the risk of overlapping of research and confusion on identification of these compounds. Several me-chanisms leading to cell death have been hypothesized. These include depletion of the proton motive force(PMF) across the cell membrane: RNase and/or DNase activity within the sensitive cell; and pore formation and lysis of sensitive cells at the cell membrane.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2885-2889
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• 2013

Goniothalamin is an active compound extracted from Goniothalamus griffithii, a local plant found in northern Thailand. Goniothalamin inhibits cancer cell growth but is also toxic to normal cells. The aims of this study were to identify the cytotoxic effect of goniothalamin and the mechanism of cell death in human HL-60 and U937 cells. Cytotoxicity was determined by MTT assay and cell cycle profiles were demonstrated by staining with propidium iodide (PI) and flow cytometry. Apoptosis was confirmed by staining with annexin V-FITC/propidium iodide (PI) and flow cytometry. Reduction of mitochondrial transmembrane potential was determined by staining with dihexyloxacarbocyanine iodide and flow cytometry and expression of Smac, caspase-8 and -9 was demonstrated by Western blotting. Goniothalamin inhibited growth of HL-60 and U937 cell lines. An increase of SubG1 phase was found in their cell cycle profiles, indicating apoptosis as the mode of cell death. Apoptosis was confirmed by the flip-flop of phosphatidylserine using annexin V-FITC/PI assay in HL60 and U937 cells in a dose response manner. Furthermore, reduction of mitochondrial transmembrane potential was found in both cell types while expression of caspase-8, -9 and Smac/Diablo was increased in HL-60 cells. Taken together, our results indicate that goniothalamin-treated human leukemic cells undergo apoptosis via intrinsic and extrinsic pathways.