Isocyanide Substitution in Acridine Orange Shifts DNA Damage-Mediated Phototoxicity to Permeabilization of the Lysosomal Membrane in Cancer Cells

In cancer therapy, immunogenic cell death eliminates tumor cells more efficiently than conventional apoptosis. During photodynamic therapy (PDT), some photosensitizer (PS) targeting lysosomes divert apoptosis to the immunologically more relevant necrosis-like cell death. Acridine orange (AO) is a PS targeting lysosome. We synthesized a new compound, 3-N,N-dimethylamino-6-isocyanoacridine (DM), a modified AO, aiming to target lysosomes better. To compare DM and AO, we studied optical properties, toxicity, cell internalization, and phototoxicity. In addition, light-mediated effects were monitored by the recently developed QUINESIn method on nuclei, and membrane stability, morphology, and function of lysosomes utilizing fluorescent probes by imaging cytometry in single cells. DM proved to be a better lysosomal marker at 405 nm excitation and lysed lysosomes more efficiently. AO injured DNA and histones more extensively than DM. Remarkably, DM’s optical properties helped visualize shockwaves of nuclear DNA released from cells during the PDT. The asymmetric polar modification of the AO leads to a new compound, DM, which has increased efficacy in targeting and disrupting lysosomes. Suitable AO modification may boost adaptive immune response making PDT more efficient.

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Damage-Associated Molecular Patterns Modulation by microRNA: Relevance on Immunogenic Cell Death and Cancer Treatment Outcome

Cancers ◽

10.3390/cancers13112566 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2566

Author(s):

María Julia Lamberti ◽

Annunziata Nigro ◽

Vincenzo Casolaro ◽

Natalia Belén Rumie Vittar ◽

Jessica Dal Col

Keyword(s):

Cell Death ◽

Tumor Cells ◽

Cell Activation ◽

Adaptive Immune Response ◽

Current Status ◽

Immunogenic Cell Death ◽

Basal Expression ◽

Antigen Presenting ◽

Molecular Patterns ◽

Damage Associated Molecular Patterns

Immunogenic cell death (ICD) in cancer is a functionally unique regulated form of stress-mediated cell death that activates both the innate and adaptive immune response against tumor cells. ICD makes dying cancer cells immunogenic by improving both antigenicity and adjuvanticity. The latter relies on the spatiotemporally coordinated release or exposure of danger signals (DAMPs) that drive robust antigen-presenting cell activation. The expression of DAMPs is often constitutive in tumor cells, but it is the initiating stressor, called ICD-inducer, which finally triggers the intracellular response that determines the kinetics and intensity of their release. However, the contribution of cell-autonomous features, such as the epigenetic background, to the development of ICD has not been addressed in sufficient depth. In this context, it has been revealed that several microRNAs (miRNAs), besides acting as tumor promoters or suppressors, can control the ICD-associated exposure of some DAMPs and their basal expression in cancer. Here, we provide a general overview of the dysregulation of cancer-associated miRNAs whose targets are DAMPs, through which new molecular mediators that underlie the immunogenicity of ICD were identified. The current status of miRNA-targeted therapeutics combined with ICD inducers is discussed. A solid comprehension of these processes will provide a framework to evaluate miRNA targets for cancer immunotherapy.

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Calreticulin—Multifunctional Chaperone in Immunogenic Cell Death: Potential Significance as a Prognostic Biomarker in Ovarian Cancer Patients

Cells ◽

10.3390/cells10010130 ◽

2021 ◽

Vol 10 (1) ◽

pp. 130

Author(s):

Michal Kielbik ◽

Izabela Szulc-Kielbik ◽

Magdalena Klink

Keyword(s):

Ovarian Cancer ◽

Cell Death ◽

Cancer Patients ◽

Tumor Cells ◽

Cytotoxic T Cells ◽

Adaptive Immune Response ◽

Ovarian Cancer Cells ◽

Immunogenic Cell Death ◽

Antigen Presenting ◽

Molecular Patterns

Immunogenic cell death (ICD) is a type of death, which has the hallmarks of necroptosis and apoptosis, and is best characterized in malignant diseases. Chemotherapeutics, radiotherapy and photodynamic therapy induce intracellular stress response pathways in tumor cells, leading to a secretion of various factors belonging to a family of damage-associated molecular patterns molecules, capable of inducing the adaptive immune response. One of them is calreticulin (CRT), an endoplasmic reticulum-associated chaperone. Its presence on the surface of dying tumor cells serves as an “eat me” signal for antigen presenting cells (APC). Engulfment of tumor cells by APCs results in the presentation of tumor’s antigens to cytotoxic T-cells and production of cytokines/chemokines, which activate immune cells responsible for tumor cells killing. Thus, the development of ICD and the expression of CRT can help standard therapy to eradicate tumor cells. Here, we review the physiological functions of CRT and its involvement in the ICD appearance in malignant disease. Moreover, we also focus on the ability of various anti-cancer drugs to induce expression of surface CRT on ovarian cancer cells. The second aim of this work is to discuss and summarize the prognostic/predictive value of CRT in ovarian cancer patients.

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Programmed Cell Death and Apoptosis in Lymphocyte Development and Function

CHEST Journal ◽

10.1378/chest.103.2_supplement.99s ◽

1993 ◽

Vol 103 (2) ◽

pp. 99S-101S ◽

Cited By ~ 18

Author(s):

J.John Cohen

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Lymphocyte Development ◽

And Function

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IREN, a novel EF-hand motif-containing nuclease, functions in the degradation of nuclear DNA during the hypersensitive response cell death in rice

Bioscience Biotechnology and Biochemistry ◽

10.1080/09168451.2015.1123610 ◽

2016 ◽

Vol 80 (4) ◽

pp. 748-760 ◽

Cited By ~ 2

Author(s):

Yuka Ootsubo ◽

Takanori Hibino ◽

Takahito Wakazono ◽

Yukio Mukai ◽

Fang-Sik Che

Keyword(s):

Cell Death ◽

Hypersensitive Response ◽

Nuclear Dna ◽

Ef Hand

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Detection of cell death in human skin wounds of various ages by an in situ end labeling of nuclear DNA fragments

International Journal of Legal Medicine ◽

10.1007/s004140050078 ◽

1997 ◽

Vol 110 (5) ◽

pp. 240-243 ◽

Cited By ~ 8

Author(s):

R. Hausmann ◽

A. Nerlich ◽

J. T�bel ◽

P. Betz ◽

I. Wiest

Keyword(s):

Cell Death ◽

Human Skin ◽

Nuclear Dna ◽

Skin Wounds ◽

Dna Fragments

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Vitamin D metabolism, sex hormones, and male reproductive function

Reproduction ◽

10.1530/rep-12-0064 ◽

2012 ◽

Vol 144 (2) ◽

pp. 135-152 ◽

Cited By ~ 35

Author(s):

Martin Blomberg Jensen

Keyword(s):

Vitamin D ◽

Association Studies ◽

Reproductive Function ◽

Hormone Production ◽

Vitamin D Metabolism ◽

Mediated Effects ◽

Male Reproductive Function ◽

Expression Studies ◽

Metabolizing Enzyme ◽

And Function

The spectrum of vitamin D (VD)-mediated effects has expanded in recent years, and VD is now recognized as a versatile signaling molecule rather than being solely a regulator of bone health and calcium homeostasis. One of the recently identified target areas of VD is male reproductive function. The VD receptor (VDR) and the VD metabolizing enzyme expression studies documented the presence of this system in the testes, mature spermatozoa, and ejaculatory tract, suggesting that both systemic and local VD metabolism may influence male reproductive function. However, it is still debated which cell is the main VD target in the testis and to what extent VD is important for sex hormone production and function of spermatozoa. This review summarizes descriptive studies on testicular VD metabolism and spatial distribution of VDR and the VD metabolizing enzymes in the mammalian testes and discusses mechanistic and association studies conducted in animals and humans. The reviewed evidence suggests some effects of VD on estrogen and testosterone biosynthesis and implicates involvement of both systemic and local VD metabolism in the regulation of male fertility potential.

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Abstract 3734: Cancer cell-targeted photoimmunotherapy elicits immunogenic cell death and activates the innate and adaptive immune response in the tumor microenvironment

10.1158/1538-7445.am2019-3734 ◽

2019 ◽

Author(s):

Michelle A. Hsu ◽

Stephanie M. Okamura ◽

Daniele M. Bergeron ◽

Deepak Yadav ◽

Jerry J. Fong ◽

...

Keyword(s):

Immune Response ◽

Cell Death ◽

Tumor Microenvironment ◽

Cancer Cell ◽

Adaptive Immune Response ◽

Immunogenic Cell Death ◽

Adaptive Immune

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Mechanisms of programmed cell death

Journal of Applied Biotechnology & Bioengineering ◽

10.15406/jabb.2019.06.00188 ◽

2019 ◽

Vol 6 (4) ◽

pp. 156-158

Author(s):

Abdu-Alhameed A Ali Azzwali ◽

Azab Elsayed Azab

Keyword(s):

Dna Damage ◽

Cell Death ◽

Programmed Cell Death ◽

Nuclear Dna ◽

Chromatin Condensation ◽

Cell Shrinkage ◽

Membrane Blebbing ◽

Development And Aging ◽

Nuclear Dna Fragmentation ◽

Dependent Pathway

The present review aims to spotlight on the mechanisms and stages of programmed cell death. Apoptosis, known as programmed cell death, is a homeostatic mechanism that generally occurs during development and aging in order to keep cells in tissue. It can also act as a protective mechanism, for example, in immune response or if cells are damaged by toxin agents or diseases. In cancer treatment, drugs and irradiation used in chemotherapy leads to DNA damage, which results in triggering apoptosis through the p53 dependent pathway in cancer treatment, drugs and irradiation used in chemotherapy leads to DNA damage, which results in triggering apoptosis through the p53 dependent pathway. Corticosteroids can cause apoptotic death in a number of cells. A number of changes in cell morphology are related to the different stages of apoptosis, which includes nuclear DNA fragmentation, cell shrinkage, chromatin condensation, membrane blebbing, and the formation of apoptotic bodies. There are three pathways for apoptosis, the intrinsic (mitochondrial) and extrinsic (death receptor) are the two major paths that are interlinked and that can effect one another. Conclusion: It can be concluded that apoptosis is a homeostatic mechanism that generally occurs during development and aging in order to keep cells in tissue. Drugs and irradiation used in chemotherapy leads to DNA damage, which results in triggering apoptosis through the p53 dependent pathway. The apoptosis, stages are includes nuclear DNA fragmentation, cell shrinkage, chromatin condensation, membrane blebbing, and the formation of apoptotic bodies. There are three pathways for apoptosis.

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Cell wound repair in Drosophila occurs through three distinct phases of membrane and cytoskeletal remodeling

The Journal of Cell Biology ◽

10.1083/jcb.201011018 ◽

2011 ◽

Vol 193 (3) ◽

pp. 455-464 ◽

Cited By ~ 78

Author(s):

Maria Teresa Abreu-Blanco ◽

Jeffrey M. Verboon ◽

Susan M. Parkhurst

Keyword(s):

Cell Death ◽

Plasma Membrane ◽

Single Cell ◽

Wound Repair ◽

Single Cells ◽

Repair Process ◽

Wound Edge ◽

Cytoskeletal Remodeling ◽

Tissue Integrity ◽

E Cadherin

When single cells or tissues are injured, the wound must be repaired quickly in order to prevent cell death, loss of tissue integrity, and invasion by microorganisms. We describe Drosophila as a genetically tractable model to dissect the mechanisms of single-cell wound repair. By analyzing the expression and the effects of perturbations of actin, myosin, microtubules, E-cadherin, and the plasma membrane, we define three distinct phases in the repair process—expansion, contraction, and closure—and identify specific components required during each phase. Specifically, plasma membrane mobilization and assembly of a contractile actomyosin ring are required for this process. In addition, E-cadherin accumulates at the wound edge, and wound expansion is excessive in E-cadherin mutants, suggesting a role for E-cadherin in anchoring the actomyosin ring to the plasma membrane. Our results show that single-cell wound repair requires specific spatial and temporal cytoskeleton responses with distinct components and mechanisms required at different stages of the process.

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