scholarly journals Targeting of Prosurvival Pathways as Therapeutic Approaches against Primary Effusion Lymphomas: Past, Present, and Future

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Marisa Granato ◽  
Roberta Santarelli ◽  
Roberta Gonnella ◽  
Antonella Farina ◽  
Pankaj Trivedi ◽  
...  
Keyword(s):  
Cell Death ◽  
Dendritic Cell ◽  
B Cell ◽  
Cancer Cells ◽  
Side Effect ◽  
Cytotoxic Effect ◽  
Anticancer Therapy ◽  
Therapeutic Approaches ◽  
Potential Side Effect ◽  
Primary Effusion Lymphomas

Constitutively activated prosurvival pathways render cancer cells addicted to their effects. Consequently they turn out to be the Achilles’ heels whose inhibition can be exploited in anticancer therapy. Primary effusion lymphomas (PELs) are very aggressive non-Hodgkin’s B cell lymphomas, whose pathogenesis is strictly linked to Kaposi’s sarcoma herpesvirus (KSHV) infection. Here we summarized previous studies from our and other laboratories exploring the cytotoxic effect of drugs inhibiting the main prosurvival pathways activated in PEL cells. Moreover, the immunogenicity of cell death, in terms of dendritic cell (DC) activation and their potential side effect on DCs, is discussed.

scholarly journals Laser nanobubbles induce immunogenic cell death in breast cancer

Nanoscale ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 3644-3653
Author(s):  
Hieu T. M. Nguyen ◽  
Nitesh Katta ◽  
Jessica A. Widman ◽  
Eri Takematsu ◽  
Xu Feng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Dendritic Cell ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cell Activation ◽  
Immunogenic Cell Death ◽  
Dendritic Cell Activation

Laser nanobubbles induce dendritic cell activation in breast cancer cells.

scholarly journals Effect of Calomelanone, a Dihydrochalcone Analogue, on Human Cancer Apoptosis/Regulated Cell Death in an In Vitro Model

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Wasitta Rachakhom ◽  
Ratana Banjerdpongchai
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Hepg2 Cells ◽  
Cytotoxic Effect ◽  
Human Cancer ◽  
Autophagic Flux ◽  
Dependent Manner ◽  
Anticancer Activities ◽  
Human Cancer Cells ◽  
Regulated Cell Death

Calomelanone, 2 ′ ,6 ′ -dihydroxy-4,4 ′ -dimethoxydihydrochalcone, possesses anticancer activities. This study was conducted to investigate the cytotoxic effect of calomelanone, a dihydrochalcone analogue, on human cancer cells and its associated mechanisms. The cytotoxic effect of calomelanone was measured by MTT assay. Annexin V-FITC/propidium iodide and DiOC6 staining that employed flow cytometry were used to determine the mode of cell death and reduction of mitochondrial transmembrane potential (MTP), respectively. Caspase activities were measured using specific substrates and colorimetric analysis. The expression levels of Bcl-2 family proteins were determined by immunoblotting. Reactive oxygen species were also measured using 2 ′ ,7 ′ -dihydrodichlorofluorescein diacetate and dihydroethidium (fluorescence dyes). Calomelanone was found to be toxic towards various human cancer cells, including acute promyelocytic HL-60 and monocytic leukemic U937 cells, in a dose-dependent manner at 24 h and human hepatocellular HepG2 cells at 48 h. However, the proliferation of HepG2 cells increased at 24 h. Calomelanone was found to induce apoptosis in HL-60 and U937 at 24 h and HepG2 apoptosis at 48 h via the intrinsic pathway by inducing MTP disruption. This compound also induced caspase-3, caspase-8, and caspase-9 activities. Calomelanone upregulated proapoptotic Bax and Bak and downregulated antiapoptotic Bcl-xL proteins in HepG2 cells. Moreover, signaling was also associated with oxidative stress in HepG2 cells. Calomelanone induced autophagy at 24 h of treatment, which was evidenced by staining with monodansylcadaverine (MDC) to represent autophagic flux. This was associated with a decrease of Akt (survival pathway) and an upregulation of Atg5 (the marker of autophagy). Thus, calomelanone induced apoptosis/regulated cell death in HL-60, U937, and HepG2 cells. However, it also induced autophagy in HepG2 depending on duration, dose, and type of cells. Thus, calomelanone could be used as a potential anticancer agent for cancer treatment. Nevertheless, acute and chronic toxicity should be further investigated in animals before conducting investigations in human patients.

An optimized retinoic acid-inducible gene I agonist M8 induces immunogenic cell death markers in human cancer cells and dendritic cell activation

2019 ◽  
Vol 68 (9) ◽  
pp. 1479-1492 ◽  
Author(s):  
Luciano Castiello ◽  
Alessandra Zevini ◽  
Elisabetta Vulpis ◽  
Michela Muscolini ◽  
Matteo Ferrari ◽  
...  
Keyword(s):  
Cell Death ◽  
Retinoic Acid ◽  
Dendritic Cell ◽  
Cancer Cells ◽  
Cell Activation ◽  
Human Cancer ◽  
Immunogenic Cell Death ◽  
Dendritic Cell Activation ◽  
Human Cancer Cells ◽  
Inducible Gene

The Association of Vitamins C and K3 Kills Cancer Cells Mainly by Autoschizis, a Novel Form of Cell Death. Basis of Their Potential Use as Coadjuvants in Anticancer Therapy

ChemInform ◽  
2003 ◽  
Vol 34 (33) ◽  
Author(s):  
Julien Verrax ◽  
Julie Cadrobbi ◽  
Marianne Delvaux ◽  
James M. Jamison ◽  
Jacques Gilloteaux ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Anticancer Therapy ◽  
Potential Use

scholarly journals A sequence-specific DNA binding small molecule triggers the release of immunogenic signals and phagocytosis in a model of B-cell lymphoma

2015 ◽  
Vol 48 (4) ◽  
pp. 453-464 ◽  
Author(s):  
JeenJoo S. Kang ◽  
Peter B. Dervan
Keyword(s):  
Cell Death ◽  
B Cell ◽  
Cancer Cells ◽  
Dna Sequences ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Repeat Sequence ◽  
Immunogenic Cell Death ◽  
Telomere Repeat ◽  
Molecular Patterns

AbstractMeans to cause an immunogenic cell death could lead to significant insight into how cancer escapes immune control. In this study, we screened a library of five pyrrole–imidazole polyamides coding for different DNA sequences in a model of B-cell lymphoma for the upregulation of surface calreticulin, a pro-phagocytosis signal implicated in immunogenic cell death. We found that hairpin polyamide 1 triggers the release of the damage-associated molecular patterns calreticulin, ATP and HMGB1 in a slow necrotic-type cell death. Consistent with this signaling, we observed an increase in the rate of phagocytosis by macrophages after the cancer cells were exposed to polyamide 1. The DNA sequence preference of polyamide 1 is 5′-WGGGTW-3′ (where W = A/T), indicated by the pairing rules and confirmed by the Bind-n-Seq method. The close correspondence of this sequence with the telomere-repeat sequence suggests a potential mechanism of action through ligand binding at the telomere. This study reveals a chemical means to trigger an inflammatory necrotic cell death in cancer cells.

Complement-mediated cell death induced by rituximab in B-cell lymphoproliferative disorders is mediated in vitro by a caspase-independent mechanism involving the generation of reactive oxygen species

Blood ◽  
2001 ◽  
Vol 98 (9) ◽  
pp. 2771-2777 ◽  
Author(s):  
Beatriz Bellosillo ◽  
Neus Villamor ◽  
Armando López-Guillermo ◽  
Silvia Marcé ◽  
Jordi Esteve ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
B Cell ◽  
Cytotoxic Effect ◽  
Reactive Oxygen ◽  
Lymphoproliferative Disorders ◽  
Oxygen Species ◽  
Independent Mechanism ◽  
In Cells

Abstract Mechanisms involving the in vitro effect of rituximab in cells from 55 patients with B-cell lymphoproliferative disorders were investigated. No cytotoxic effect was observed when cells were incubated with rituximab alone, but in the presence of human AB serum rituximab induced complement-dependent cell death (R-CDC). A cytotoxic effect was observed in cells from 9 of 33 patients with B-cell chronic lymphocytic leukemia, 16 of 16 patients with mantle-cell lymphoma, 4 of 4 patients with follicular lymphoma, and 2 of 2 patients with hairy-cell leukemia. R-CDC was observed in cells from patients expressing more than 50 × 103 CD20 molecules per cell, and directly correlated with the number of CD20 molecules per cell. Preincubation with anti-CD59 increased the cytotoxic effect of rituximab and sensitized cells from nonsensitive cases. Neither cleavage of poly-ADP ribose polymerase (PARP) nor activation of caspase-3 was observed in R-CDC. In addition, no cells with a hypodiploid DNA content were detected and R-CDC was not prevented by a broad-spectrum caspase inhibitor, suggesting a caspase-independent mechanism. Incubation with rituximab in the presence of AB serum induced a rapid and intense production of reactive oxygen species (ROS). R-CDC was blocked by the incubation of cells with N-acetyl-L-cysteine (NAC) or Tiron, 2 ROS scavengers, indicating that the cytotoxic effect was due to the generation of superoxide (O2−) radicals. In conclusion, the results of the present study suggest that CD20, CD59, and complement have a role in the in vitro cytotoxic effect of rituximab, which is mediated by a caspase-independent process that involves ROS generation.

scholarly journals Dehydroabietic Acid Derivative QC4 Induces Gastric Cancer Cell Death via Oncosis and Apoptosis

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Dongjun Luo ◽  
Qing Ni ◽  
Anlai Ji ◽  
Wen Gu ◽  
Junhua Wu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Cytotoxic Effect ◽  
Membrane Integrity ◽  
Dehydroabietic Acid ◽  
Protein Cleavage ◽  
Gastric Cancer Cells ◽  
Cell Membrane Integrity ◽  
Cancer Cell Death

Aim. QC4 is the derivative of rosin’s main components dehydroabietic acid (DHA). We investigated the cytotoxic effect of QC4 on gastric cancer cells and revealed the mechanisms beneath the induction of cell death.Methods. The cytotoxic effect of QC4 on gastric cancer cells was evaluated by CCK-8 assay and flow cytometry. The underlying mechanisms were tested by administration of cell death related inhibitors and detection of apoptotic and oncosis related proteins. Cytomembrane integrity and organelles damage were confirmed by lactate dehydrogenase (LDH) leakage assay, mitochondrial function test, and cytosolic free Ca2+concentration detection.Results. QC4 inhibited cell proliferation dose- and time-dependently and destroyed cell membrane integrity, activated calpain-1 autolysis, and induced apoptotic protein cleavage in gastric cancer cells. The detection of decreased ATP and mitochondrial membrane potential, ROS accumulation, and cytosolic free Ca2+elevation confirmed organelles damage in QC4-treated gastric cancer cells.Conclusions. DHA derivative QC4 induced the damage of cytomembrane and organelles which finally lead to oncosis and apoptosis in gastric cancer cells. Therefore, as a derivative of plant derived small molecule DHA, QC4 might become a promising agent in gastric cancer therapy.

scholarly journals Emerging approaches to target mitochondrial apoptosis in cancer cells

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1793 ◽  
Author(s):  
Andrew Gilmore ◽  
Louise King
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Tumour Cells ◽  
Mitochondrial Apoptosis ◽  
Therapeutic Approaches ◽  
Bh3 Mimetics ◽  
Novel Therapeutics ◽  
New Class ◽  
New Therapeutic Approaches

Apoptosis is a highly conserved programme for removing damaged and unwanted cells. Apoptosis in most cells is coordinated on mitochondria by the Bcl-2 family of proteins. The balance between pro- and anti-apoptotic Bcl-2 family proteins sets a threshold for mitochondrial apoptosis, a balance that is altered during cancer progression. Consequently, avoidance of cell death is an established cancer hallmark. Although there is a general perception that tumour cells are more resistant to apoptosis than their normal counterparts, the realities of cell death regulation in cancer are more nuanced. In this review we discuss how a profound understanding of this control has led to new therapeutic approaches, including the new class of BH3-mimetics, which directly target apoptosis as a vulnerability in cancer. We discuss recent findings that highlight the current limitations in our understanding of apoptosis and how these novel therapeutics work.

scholarly journals Immunogenic ferroptosis and where to find it?

2021 ◽  
Vol 9 (12) ◽  
pp. e003430
Author(s):  
Robin Demuynck ◽  
Iuliia Efimova ◽  
Faye Naessens ◽  
Dmitri V Krysko
Keyword(s):  
Cell Death ◽  
Dendritic Cells ◽  
Cancer Cells ◽  
Antitumor Immunity ◽  
Anticancer Therapy ◽  
Oxidized Lipids ◽  
Immunogenic Cell Death ◽  
Cross Presentation ◽  
Regulated Cell Death ◽  
Potential Use

Ferroptosis is a recently discovered form of regulated cell death that is morphologically, genetically, and biochemically distinct from apoptosis and necroptosis, and its potential use in anticancer therapy is emerging. The strong immunogenicity of (early) ferroptotic cancer cells broadens the current concept of immunogenic cell death and opens up new possibilities for cancer treatment. In particular, induction of immunogenic ferroptosis could be beneficial for patients with cancers resistant to apoptosis and necroptosis. However, ferroptotic cancer cells may be a rich source of oxidized lipids, which contribute to decreased phagocytosis and antigen cross-presentation by dendritic cells and thus may favor tumor evasion. This could explain the non-immunogenicity of late ferroptotic cells. Besides the presence of lactate in the tumor microenvironment, acidification and hypoxia are essential factors promoting ferroptosis resistance and affecting its immunogenicity. Here, we critically discuss the crucial mediators controlling the immunogenicity of ferroptosis that modulate the induction of antitumor immunity. We emphasize that it will be necessary to also identify the tolerogenic (ie, immunosuppressive) nature of ferroptosis, which can lead to tumor evasion.

scholarly journals Current Clinical Applications and Future Perspectives of Immune Checkpoint Inhibitors in Non-Hodgkin Lymphoma

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
John Apostolidis ◽  
Ayman Sayyed ◽  
Mohammed Darweesh ◽  
Panayotis Kaloyannidis ◽  
Hani Al Hashmi
Keyword(s):  
Clinical Trials ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Programmed Cell Death ◽  
B Cell ◽  
Cancer Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors

Cancer cells escape immune recognition by exploiting the programmed cell-death protein 1 (PD-1)/programmed cell-death 1 ligand 1 (PD-L1) immune checkpoint axis. Immune checkpoint inhibitors that target PD-1/PD-L1 unleash the properties of effector T cells that are licensed to kill cancer cells. Immune checkpoint blockade has dramatically changed the treatment landscape of many cancers. Following the cancer paradigm, preliminary results of clinical trials in lymphoma have demonstrated that immune checkpoint inhibitors induce remarkable responses in specific subtypes, most notably classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma, while in other subtypes, the results vary considerably, from promising to disappointing. Lymphomas that respond to immune checkpoint inhibitors tend to exhibit tumor cells that reside in a T-cell-rich immune microenvironment and display constitutive transcriptional upregulation of genes that facilitate innate immune resistance, such as structural variations of the PD-L1 locus, collectively referred to as T-cell-inflamed lymphomas, while those lacking such characteristics are referred to as noninflamed lymphomas. This distinction is not necessarily a sine qua non of response to immune checkpoint inhibitors, but rather a framework to move the field forward with a more rational approach. In this article, we provide insights on our current understanding of the biological mechanisms of immune checkpoint evasion in specific subtypes of B-cell and T-cell non-Hodgkin lymphomas and summarize the clinical experience of using inhibitors that target immune checkpoints in these subtypes. We also discuss the phenomenon of hyperprogression in T-cell lymphomas, related to the use of such inhibitors when T cells themselves are the target cells, and consider future approaches to refine clinical trials with immune checkpoint inhibitors in non-Hodgkin lymphomas.

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