scholarly journals The caspase-3/GSDME signal pathway as a switch between apoptosis and pyroptosis in cancer

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Mingxia Jiang ◽  
Ling Qi ◽  
Lisha Li ◽  
Yanjing Li
Keyword(s):  
Cell Death ◽  
Tumor Cell ◽  
Caspase 3 ◽  
Suppressor Gene ◽  
Signal Pathway ◽  
Cell Swelling ◽  
Tumor Cell Death ◽  
Cell Death Pathways ◽  
Apoptotic Pathways ◽  
New Strategies

Abstract Apoptosis has long been recognized as a mechanism that kills the cancer cells by cytotoxic drugs. In recent years, studies have proved that pyroptosis can also shrink tumors and inhibit cells proliferation. Both apoptosis and pyroptosis are caspase-dependent programmed cell death pathways. Cysteinyl aspartate specific proteinase-3 (Caspase-3) is a common key protein in the apoptosis and pyroptosis pathways, and when activated, the expression level of tumor suppressor gene Gasdermin E (GSDME) determines the mechanism of tumor cell death. When GSDME is highly expressed, the active caspase-3 cuts it and releases the N-terminal domain to punch holes in the cell membrane, resulting in cell swelling, rupture, and death. When the expression of GSDME is low, it will lead to the classical mechanism of tumor cell death, which is apoptosis. More interestingly, researchers have found that GSDME can also be located upstream of caspase-3, connecting extrinsic, and intrinsic apoptotic pathways. Then, promoting caspase-3 activation, and forming a self-amplifying feed-forward loop. GSDME-mediated pyroptosis is correlated with the side effects of chemotherapy and anti-tumor immunity. This article mainly reviews the caspase-3/GSDME signal pathway as a switch between apoptosis and pyroptosis in cancer, to provide new strategies and targets for cancer treatment.

scholarly journals Novel chemical compound SINCRO with dual function in STING ‐type I interferon and tumor cell death pathways

2018 ◽  
Vol 109 (9) ◽  
pp. 2687-2696 ◽  
Author(s):  
Yoshitaka Kimura ◽  
Hideo Negishi ◽  
Atsushi Matsuda ◽  
Nobuyasu Endo ◽  
Sho Hangai ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Cell ◽  
Chemical Compound ◽  
Type I Interferon ◽  
Dual Function ◽  
Type I ◽  
Tumor Cell Death ◽  
Cell Death Pathways

scholarly journals Positive allosteric modulation of P2X7 promotes apoptotic cell death over lytic cell death responses in macrophages

2019 ◽  
Vol 10 (12) ◽  
Author(s):  
Stefan Bidula ◽  
Kshitija Dhuna ◽  
Ray Helliwell ◽  
Leanne Stokes
Keyword(s):  
Cell Death ◽  
Mitochondrial Membrane ◽  
Caspase 3 ◽  
Allosteric Modulation ◽  
Cell Swelling ◽  
Dependent Manner ◽  
Apoptosis Pathway ◽  
Membrane Rupture ◽  
Cell Death Pathways ◽  
Intrinsic Apoptosis Pathway

AbstractP2X7 is an ATP-gated ion channel that is highly expressed by leukocytes, such as macrophages. Here, P2X7 has been demonstrated to be involved in the regulation of various cell death pathways; including apoptosis, pyroptosis, necrosis, and autophagy. However, cell death induction via P2X7 is complex and is reliant upon the nature of the stimulus, the duration of the stimulus, and the cell type investigated. Previous reports state that high extracellular ATP concentrations promote osmotic lysis, but whether positive allosteric modulation of P2X7 in the presence of lower concentrations of ATP condemns cells to the same fate is unknown. In this study, we compared cell death induced by high ATP concentrations, to cell death induced by compound K, a recently identified and potent positive allosteric modulator of P2X7. Based on our observations, we propose that high ATP concentrations induce early cell swelling, loss of mitochondrial membrane potential, plasma membrane rupture, and LDH release. Conversely, positive allosteric modulation of P2X7 primarily promotes an intrinsic apoptosis pathway. This was characterised by an increase in mitochondrial Ca2+, accelerated production of mitochondrial ROS, loss of mitochondrial membrane permeability in a Bax-dependent manner, the potential involvement of caspase-1, and caspase-3, and significantly accelerated kinetics of caspase-3 activation. This study highlights the ability of positive allosteric modulators to calibrate P2X7-dependent cell death pathways and may have important implications in modulating the antimicrobial immune response and in the resolution of inflammation.

Biodegradable Porous Silicon Nanocontainers as an Effective Drug Carrier for Regulation of the Tumor Cell Death Pathways

2019 ◽  
Vol 5 (11) ◽  
pp. 6063-6071 ◽  
Author(s):  
Polina V. Maximchik ◽  
Konstantin Tamarov ◽  
Eugene V. Sheval ◽  
Elen Tolstik ◽  
Tatiana Kirchberger-Tolstik ◽  
...  
Keyword(s):  
Cell Death ◽  
Porous Silicon ◽  
Tumor Cell ◽  
Drug Carrier ◽  
Effective Drug ◽  
Tumor Cell Death ◽  
Cell Death Pathways

scholarly journals Cellular cytotoxicity is a form of immunogenic cell death

2020 ◽  
Vol 8 (1) ◽  
pp. e000325 ◽  
Author(s):  
Luna Minute ◽  
Alvaro Teijeira ◽  
Alfonso R Sanchez-Paulete ◽  
Maria C Ochoa ◽  
Maite Alvarez ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Dendritic Cells ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Cd8 T Cells ◽  
Immunogenic Cell Death ◽  
Cell Debris ◽  
Tumor Cell Death ◽  
Mhc Multimer

BackgroundThe immune response to cancer is often conceptualized with the cancer immunity cycle. An essential step in this interpretation is that antigens released by dying tumors are presented by dendritic cells to naive or memory T cells in the tumor-draining lymph nodes. Whether tumor cell death resulting from cytotoxicity, as mediated by T cells or natural killer (NK) lymphocytes, is actually immunogenic currently remains unknown.MethodsIn this study, tumor cells were killed by antigen-specific T-cell receptor (TCR) transgenic CD8 T cells or activated NK cells. Immunogenic cell death was studied analyzing the membrane exposure of calreticulin and the release of high mobility group box 1 (HMGB1) by the dying tumor cells. Furthermore, the potential immunogenicity of the tumor cell debris was evaluated in immunocompetent mice challenged with an unrelated tumor sharing only one tumor-associated antigen and by class I major histocompatibility complex (MHC)-multimer stainings. Mice deficient inBatf3,Ifnar1andSting1were used to study mechanistic requirements.ResultsWe observe in cocultures of tumor cells and effector cytotoxic cells, the presence of markers of immunogenic cell death such as calreticulin exposure and soluble HMGB1 protein. Ovalbumin (OVA)-transfected MC38 colon cancer cells, exogenously pulsed to present the gp100 epitope are killed in culture by mouse gp100-specific TCR transgenic CD8 T cells. Immunization of mice with the resulting destroyed cells induces epitope spreading as observed by detection of OVA-specific T cells by MHC multimer staining and rejection of OVA+EG7 lymphoma cells. Similar results were observed in mice immunized with cell debris generated by NK-cell mediated cytotoxicity. Mice deficient inBatf3-dependent dendritic cells (conventional dendritic cells type 1, cDC1) fail to develop an anti-OVA response when immunized with tumor cells killed by cytotoxic lymphocytes. In line with this, cultured cDC1 dendritic cells uptake and can readily cross-present antigen from cytotoxicity-killed tumor cells to cognate CD8+T lymphocytes.ConclusionThese results support that an ongoing cytotoxic antitumor immune response can lead to immunogenic tumor cell death.

Photodynamic Therapy with Liposomal Zinc Phthalocyanine and Tirapazamine Increases Tumor Cell Death via DNA Damage

2017 ◽  
Vol 13 (2) ◽  
pp. 204-220 ◽  
Author(s):  
Mans Broekgaarden ◽  
Ruud Weijer ◽  
AlbertC. van Wijk ◽  
RuudC. Cox ◽  
MaartenR. Egmond ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Photodynamic Therapy ◽  
Tumor Cell ◽  
Zinc Phthalocyanine ◽  
Tumor Cell Death

New marker of tumor cell death revealed by ATR-FTIR spectroscopy

2011 ◽  
Vol 399 (8) ◽  
pp. 2771-2778 ◽  
Author(s):  
Lucia Di Giambattista ◽  
Deleana Pozzi ◽  
Paola Grimaldi ◽  
Silvia Gaudenzi ◽  
Stefania Morrone ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Cell ◽  
Ftir Spectroscopy ◽  
Tumor Cell Death
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