Mechanisms of resistance of normal cells to TRAIL induced apoptosis vary between different cell types

The review presents the main and additional features that distinguish tumor cells from normal tissue cells. They include sustained proliferative signaling, evasion from growth suppressors, resisting cell death, enabling replicative immortality, angiogenesis induction, and invasion and metastasis activation. Basis for the formation of these features is provided by tumor genome instability. Tumors are complex tissues that consist of different cell types interacting with each other as well as with normal cells. An important characteristic of tumor cells is the ability to interact with the tumor microenvironment and the formation of tumor stroma.

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Early Induction of Apoptosis in Hematopoietic Cell Lines After Exposure to Flavopiridol

Blood ◽

10.1182/blood.v91.2.458 ◽

1998 ◽

Vol 91 (2) ◽

pp. 458-465 ◽

Cited By ~ 149

Author(s):

Bernard W. Parker ◽

Gurmeet Kaur ◽

Wilberto Nieves-Neira ◽

Mohammed Taimi ◽

Glenda Kohlhagen ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Cell Lines ◽

Prostate Carcinoma ◽

Cell Types ◽

Carcinoma Cells ◽

Cycle Arrest ◽

Induced Apoptosis ◽

Different Cell Types ◽

Hematopoietic Cell Lines

Abstract Flavopiridol (NSC 649890; Behringwerke L86-8275, Marburg, Germany), is a potent inhibitor of cyclin dependent kinases (CDKs) 1, 2, and 4. It has potent antiproliferative effects in vitro and is active in tumor models in vivo. While surveying the effect of flavopiridol on cell cycle progression in different cell types, we discovered that hematopoietic cell lines, including SUDHL4, SUDHL6 (B-cell lines), Jurkat, and MOLT4 (T-cell lines), and HL60 (myeloid), displayed notable sensitivity to flavopiridol-induced apoptosis. For example, after 100 nmol/L for 12 hours, SUDHL4 cells displayed a similar degree of DNA fragmentation to that shown by the apoptosis-resistant PC3 prostate carcinoma cells only after 3,000 nmol/L for 48 hours. After exposure to 1,000 nmol/L flavopiridol for 12 hours, typical apoptotic morphology was observed in SUDHL4 cells, but not in PC3 prostate carcinoma cells despite comparable potency (SUDHL4:120 nmol/L; PC3: 203 nmol/L) in causing growth inhibition by 50% (IC50). Flavopiridol did not induce topoisomerase I or II cleavable complex activity. A relation of p53, bcl2, or bax protein levels to apoptosis in SUDHL4 was not appreciated. While flavopiridol caused cell cycle arrest with decline in CDK1 activity in PC3 cells, apoptosis of SUDHL4 cells occurred without evidence of cell cycle arrest. These results suggest that antiproliferative activity of flavopiridol (manifest by cell cycle arrest) may be separated in different cell types from a capacity to induce apoptosis. Cells from hematopoietic neoplasms appear in this limited sample to be very susceptible to flavopiridol-induced apoptosis and therefore clinical trials in hematopoietic neoplasms should be of high priority.

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The Inhibition of EV71 Virus-Induced Apoptosis by ZVAD Through ROS and mTOR Pathway

10.21203/rs.3.rs-105123/v1 ◽

2020 ◽

Author(s):

Tiantian Xu ◽

Yinghua Li ◽

Min Guo ◽

Mingqi Zhao ◽

Haiyang Chen ◽

...

Keyword(s):

Enterovirus 71 ◽

Cell Types ◽

Antiviral Effect ◽

Vero Cells ◽

Mtor Signaling Pathway ◽

Inflammatory Reactions ◽

Induced Apoptosis ◽

Different Cell Types ◽

Antiviral Role ◽

Inflammation Cytokines

Abstract Background: Emerging evidence that Enterovirus 71 (EV71) infection closely related to infection with the generation of apoptosis. Excess apoptosis exacerbates inflammatory reactions and can even result in the death of the cell. The ZVAD is a broad caspase inhibitor, can prevent apoptosis and regulate the survival in many different cell types. Methods: The aims of this project were to elucidate the mechanism of the ZVAD in anti-EV71 virus.Results: Our data showed that reduced viral replication was observed after treated with ZVAD in EV71 infected Vero and SK-N-SH cells. Meanwhile, Vero and SK-N-SH cells infected with EV71virus were both exhibit higher cells viability in the presence of ZVAD. Additionally, ZVAD can decrease the apoptosis, ROS and inflammation induced by EV71 in the infected Vero cells. However, ZVAD may play an antiviral role in SK-N-SH cells through the mTOR signaling pathwayConclusions: In addition to inhibiting caspase, ZVAD also inhibits apoptosis by regulating ROS and inflammation cytokines to achieve antiviral effect.

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Sustained hyposmotic stress induces cell death: apoptosis by defeat

AJP Cell Physiology ◽

10.1152/ajpcell.2001.281.5.c1716 ◽

2001 ◽

Vol 281 (5) ◽

pp. C1716-C1726 ◽

Cited By ~ 7

Author(s):

Tina Jäckle ◽

Cornelia Hasel ◽

Ingo Melzner ◽

S. Brüderlein ◽

Peter M. Jehle ◽

...

Keyword(s):

Human Kidney ◽

Cell Types ◽

Surface Expression ◽

Carcinoma Cells ◽

Mitochondrial Mass ◽

Hyposmotic Stress ◽

Stressed Cells ◽

Induced Apoptosis ◽

Different Cell Types ◽

Ht 29

We describe sustained hyposmotic stress as a novel type of environmental condition enforcing apoptosis. In a dose- and time-dependent fashion, hyposmotic stress leads to a delayed type of apoptosis with considerable variations in constitutive sensitivity among different cell types. For example, after 48 h at 84 mosmol/l, the death rate ranged from 10.8 ± 0.7% in AsPc1 human pancreatic carcinoma cells to 72.0 ± 1.6% in HK-2 human kidney tubule cells. Caspase inhibitors rendered cells more resistant to hyposmolar stress; the caspase 3 inhibitor Ac-Asp-Glu-Val-aspartic acid aldehyde was the most efficient. After 24 h of stress, HT-29 colon carcinoma and HK-2 cells had increased their mitochondrial mass. This went along with an increase in mitochondrial membrane potential in HT-29 cells but with a decrease in HK-2 cells. Starting at 2 h of stress, we detected transient CD95L transcription followed by surface expression of CD95L in HT-29 but not in HK-2 cells. Inhibitory CD95L antibody partially inhibited specific death in HT-29 but not in HK-2 cells. Thus, as in other types of stress-induced apoptosis, the CD95/CD95L system is one of the different routes to suicide optionally used by hyposmotically stressed cells. Our findings may have clinical implications for the prevention and treatment of tissue damage caused by severe hyposmolar states.

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Early Induction of Apoptosis in Hematopoietic Cell Lines After Exposure to Flavopiridol

Blood ◽

10.1182/blood.v91.2.458.458_458_465 ◽

1998 ◽

Vol 91 (2) ◽

pp. 458-465 ◽

Cited By ~ 4

Author(s):

Bernard W. Parker ◽

Gurmeet Kaur ◽

Wilberto Nieves-Neira ◽

Mohammed Taimi ◽

Glenda Kohlhagen ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Cell Lines ◽

Prostate Carcinoma ◽

Cell Types ◽

Carcinoma Cells ◽

Cycle Arrest ◽

Induced Apoptosis ◽

Different Cell Types ◽

Hematopoietic Cell Lines

Flavopiridol (NSC 649890; Behringwerke L86-8275, Marburg, Germany), is a potent inhibitor of cyclin dependent kinases (CDKs) 1, 2, and 4. It has potent antiproliferative effects in vitro and is active in tumor models in vivo. While surveying the effect of flavopiridol on cell cycle progression in different cell types, we discovered that hematopoietic cell lines, including SUDHL4, SUDHL6 (B-cell lines), Jurkat, and MOLT4 (T-cell lines), and HL60 (myeloid), displayed notable sensitivity to flavopiridol-induced apoptosis. For example, after 100 nmol/L for 12 hours, SUDHL4 cells displayed a similar degree of DNA fragmentation to that shown by the apoptosis-resistant PC3 prostate carcinoma cells only after 3,000 nmol/L for 48 hours. After exposure to 1,000 nmol/L flavopiridol for 12 hours, typical apoptotic morphology was observed in SUDHL4 cells, but not in PC3 prostate carcinoma cells despite comparable potency (SUDHL4:120 nmol/L; PC3: 203 nmol/L) in causing growth inhibition by 50% (IC50). Flavopiridol did not induce topoisomerase I or II cleavable complex activity. A relation of p53, bcl2, or bax protein levels to apoptosis in SUDHL4 was not appreciated. While flavopiridol caused cell cycle arrest with decline in CDK1 activity in PC3 cells, apoptosis of SUDHL4 cells occurred without evidence of cell cycle arrest. These results suggest that antiproliferative activity of flavopiridol (manifest by cell cycle arrest) may be separated in different cell types from a capacity to induce apoptosis. Cells from hematopoietic neoplasms appear in this limited sample to be very susceptible to flavopiridol-induced apoptosis and therefore clinical trials in hematopoietic neoplasms should be of high priority.

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TNF Signaling Dictates Myeloid and Non-Myeloid Cell Crosstalk to Execute MCMV-Induced Extrinsic Apoptosis

Viruses ◽

10.3390/v12111221 ◽

2020 ◽

Vol 12 (11) ◽

pp. 1221

Author(s):

Pratyusha Mandal ◽

A. Louise McCormick ◽

Edward S. Mocarski

Keyword(s):

Cell Death ◽

Death Receptor ◽

Myeloid Cells ◽

Myeloid Cell ◽

Cell Types ◽

Murine Cytomegalovirus ◽

Caspase 8 ◽

Caspase 7 ◽

Induced Apoptosis ◽

Different Cell Types

Cytomegaloviruses all encode the viral inhibitor of caspase-8-induced apoptosis (vICA). After binding to this initiator caspase, vICA blocks caspase-8 proteolytic activity and ability to activate caspase-3 and/or caspase-7. In this manner, vICA has long been known to prevent apoptosis triggered via tumor necrosis factor (TNF) family death receptor-dependent extrinsic signaling. Here, we employ fully wild-type murine cytomegalovirus (MCMV) and vICA-deficient MCMV (∆M36) to investigate the contribution of TNF signaling to apoptosis during infection of different cell types. ∆M36 shows the expected ability to kill mouse splenic hematopoietic cells, bone marrow-derived macrophages (BMDM), and dendritic cells (BMDC). Antibody blockade or genetic elimination of TNF protects myeloid cells from death, and caspase-8 activation accompanies cell death. Interferons, necroptosis, and pyroptotic gasdermin D (GSDMD) do not contribute to myeloid cell death. Human and murine fibroblasts or murine endothelial cells (SVEC4-10) normally insensitive to TNF become sensitized to ∆M36-induced apoptosis when treated with TNF or TNF-containing BMDM-conditioned medium. We demonstrate that myeloid cells are the natural source of TNF that triggers apoptosis in either myeloid (autocrine) or non-myeloid cells (paracrine) during ∆M36 infection of mice. Caspase-8 suppression by vICA emerges as key to subverting innate immune elimination of a wide variety of infected cell types.

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Comparative Analysis of the Different Dyes’ Potential to Assess Human Normal and Cancer Cell Viability In Vitro under Different D/H Ratios in a Culture Medium

The Scientific World JOURNAL ◽

10.1155/2020/2373021 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

I. A. Zlatskiy ◽

A. V. Zlatska ◽

N. V. Antipova ◽

S. A. Dolenko ◽

I. M. Gordiienko ◽

...

Keyword(s):

Comparative Analysis ◽

Cell Viability ◽

Culture Medium ◽

Cell Types ◽

Laser Diffraction ◽

Normal Cells ◽

New Approach ◽

Medium System ◽

Different Cell Types

In this study, using new approach (laser diffraction + biological dyes), we have demonstrated the decrease of cells viability in vitro in the deuterated growth medium, whereas in the deuterium-depleted medium, there was an increase of cell viability. We have also found that not all dyes are equally sensitive to the D/H ratios in the culture medium (system) as well as to the different cell types (cancer vs normal cells).

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Mitochondria play an important role in 17β-estradiol attenuation of H2O2-induced rat endothelial cell apoptosis

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00413.2006 ◽

2007 ◽

Vol 292 (2) ◽

pp. E585-E593 ◽

Cited By ~ 29

Author(s):

Ailing Lu ◽

Michael Frink ◽

Mashkoor A. Choudhry ◽

William J. Hubbard ◽

Loring W. Rue ◽

...

Keyword(s):

Endothelial Cells ◽

Cell Types ◽

Protective Effects ◽

Caspase 9 ◽

Cytochrome C Release ◽

Potent Inducer ◽

Apoptotic Effect ◽

17Β Estradiol ◽

Induced Apoptosis ◽

Different Cell Types

Studies have shown salutary effects of 17β-estradiol following trauma-hemorrhage on different cell types. 17β-Estradiol also induces improved circulation via relaxation of the aorta and has an anti-apoptotic effect on endothelial cells. Because mitochondria play a pivotal role in apoptosis, we hypothesized that 17β-estradiol will maintain mitochondrial function and will have protective effects against H2O2-induced apoptosis in endothelial cells. Endothelial cells were isolated from rats' aorta and cultured in the presence or absence of H2O2, a potent inducer of apoptosis. In additional studies, endothelial cells were pretreated with 17β-estradiol. Flow cytometry analysis revealed H2O2-induced apoptosis in 80.9% of endothelial cells; however, prior treatment of endothelial cells with 17β-estradiol resulted in an ∼40% reduction in apoptosis. This protective effect of 17β-estradiol was abrogated when endothelial cells were cultured in the presence ICI-182780, indicating the involvement of estrogen receptor (ER). Fluorescence microscopy revealed a 17β-estradiol-mediated attenuation of H2O2-induced mitochondrial condensation. Western blot analysis demonstrated that H2O2-induced cytochrome c release from mitochondrion to cytosol and the activation of caspase-9 and -3 were decreased by 17β-estradiol. These findings suggest that 17β-estradiol attenuated H2O2-induced apoptosis via ER-dependent activation of caspase-9 and -3 in rat endothelial cells through mitochondria.

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Study of the Molecular Architecture of Keratin Filaments by Electron Microscopy

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100053310 ◽

1982 ◽

Vol 40 ◽

pp. 118-119

Author(s):

U. Aebi ◽

P. Rew ◽

T.-T. Sun

Keyword(s):

Electron Microscopy ◽

Structural Organization ◽

Cell Types ◽

Structural Features ◽

Molecular Architecture ◽

The Past ◽

Keratin Filaments ◽

Different Types ◽

10 Nm Filaments ◽

Different Cell Types

Various types of intermediate-sized (10-nm) filaments have been found and described in many different cell types during the past few years. Despite the differences in the chemical composition among the different types of filaments, they all yield common structural features: they are usually up to several microns long and have a diameter of 7 to 10 nm; there is evidence that they are made of several 2 to 3.5 nm wide protofilaments which are helically wound around each other; the secondary structure of the polypeptides constituting the filaments is rich in ∞-helix. However a detailed description of their structural organization is lacking to date.

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Processing and Characterization of Recombinant von Willebrand Factor Expressed in Different Cell Types Using a Vaccinia Virus Vector

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648398 ◽

1992 ◽

Vol 67 (01) ◽

pp. 154-160 ◽

Cited By ~ 14

Author(s):

P Meulien ◽

M Nishino ◽

C Mazurier ◽

K Dott ◽

G Piétu ◽

...

Keyword(s):

Vaccinia Virus ◽

Von Willebrand Factor ◽

Human Fibroblasts ◽

Active Form ◽

Cell Types ◽

Biologically Active ◽

L Cells ◽

Von Willebrand ◽

Different Cell Types ◽

Willebrand Factor

SummaryThe cloning of the cDNA encoding von Willebrand factor (vWF) has revealed that it is synthesized as a large precursor (pre-pro-vWF) molecule and it is now clear that the prosequence or vWAgll is responsible for the intracellular multimerization of vWF. We have cloned the complete vWF cDNA and expressed it using a recombinant vaccinia virus as vector. We have characterized the structure and function of the recombinant vWF (rvWF) secreted from five different cell types: baby hamster kidney (BHK), Chinese hamster ovary (CHO), human fibroblasts (143B), mouse fibroblasts (L) and primary embryonic chicken cells. Forty-eight hours after infection, the quantity of vWF antigen found in the cell supernatant varied from 3 to 12 U/dl depending on the cell type. By SDS-agarose gel electrophoresis, the percentage of high molecular weight forms of vWF varied from 39 to 49% relative to normal plasma for BHK, CHO, 143B and chicken cells but was less than 10% for L cells. In all cell types, the two anodic subbands of each multimer were missing. The two cathodic subbands were easily detected only in BHK and L cells. By SDS-PAGE of reduced samples, pro-vWF was present in similar quantity to the fully processed vWF subunit in L cells, present in moderate amounts in BHK and CHO and in very low amounts in 143B and chicken cells. rvWF from all cells bound to collagen and to platelets in the presence of ristocetin, the latter showing a high correlation between binding efficiency and degree of multimerization. rvWF from all cells was also shown to bind to purified FVIII and in this case binding appeared to be independent of the degree of multimerization. We conclude that whereas vWF is naturally synthesized only by endothelial cells and megakaryocytes, it can be expressed in a biologically active form from various other cell types.

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