scholarly journals The Role of Apoptosis as a Double-Edge Sword in Cancer

2021 ◽  
Author(s):  
Reyhaneh Farghadani ◽  
Rakesh Naidu
Keyword(s):  
Cell Death ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Master Regulators ◽  
Double Edge ◽  
Anti Cancer ◽  
Cancer Initiation ◽  
Double Edge Sword ◽  
Apoptotic Pathways

The pathogenesis of many diseases is most closely related to inappropriate apoptosis (either too little or too much) and cancer is one of the situations where too little apoptosis happens, leading to malignant cells that highly proliferate. Defects at any points along apoptotic pathways may lead to malignant transformation of the affected cells, tumor metastasis, and resistance to anti-cancer drugs. Several major molecular mechanisms are involved in the evasion of apoptosis in cancer initiation and progression. Bcl-2 family of proteins and caspases are the central players in the apoptotic mechanism and regulate cell death. Their imperfections cause to the deficient apoptotic signaling and thereby the inadequate apoptosis in cancer cells and eventually carcinogenesis. Strategies targeting these master regulators in carcinoma cells has been a major focus of interest in cancer studies. Therefore, despite being the cause of problem, apoptosis can be targeted in cancer therapy. This chapter provides a comprehensive review of apoptotic cell death and how deficiencies in apoptotic master regulators, caspases and Bcl-2 family proteins, influence carcinogenesis and can be targeted in cancer treatment.

scholarly journals On the Anti-Cancer Effect of Cold Atmospheric Plasma and the Possible Role of Catalase-Dependent Apoptotic Pathways

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2330
Author(s):  
Charlotta Bengtson ◽  
Annemie Bogaerts
Keyword(s):  
Mathematical Model ◽  
Cell Death ◽  
Apoptotic Cell ◽  
Atmospheric Plasma ◽  
Cold Atmospheric Plasma ◽  
Cancer Cell Death ◽  
Anti Cancer ◽  
Apoptotic Pathways ◽  
Cell Signaling Pathways

Cold atmospheric plasma (CAP) is a promising new agent for (selective) cancer treatment, but the underlying cause of the anti-cancer effect of CAP is not well understood yet. Among different theories and observations, one theory in particular has been postulated in great detail and consists of a very complex network of reactions that are claimed to account for the anti-cancer effect of CAP. Here, the key concept is a reactivation of two specific apoptotic cell signaling pathways through catalase inactivation caused by CAP. Thus, it is postulated that the anti-cancer effect of CAP is due to its ability to inactivate catalase, either directly or indirectly. A theoretical investigation of the proposed theory, especially the role of catalase inactivation, can contribute to the understanding of the underlying cause of the anti-cancer effect of CAP. In the present study, we develop a mathematical model to analyze the proposed catalase-dependent anti-cancer effect of CAP. Our results show that a catalase-dependent reactivation of the two apoptotic pathways of interest is unlikely to contribute to the observed anti-cancer effect of CAP. Thus, we believe that other theories of the underlying cause should be considered and evaluated to gain knowledge about the principles of CAP-induced cancer cell death.

scholarly journals Cell Death and Ageing – A Question of Cell Type

2002 ◽  
Vol 2 ◽  
pp. 943-948 ◽  
Author(s):  
Pidder Jansen-Dürr
Keyword(s):  
Cell Death ◽  
Molecular Mechanisms ◽  
Replicative Senescence ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Ageing Process ◽  
Human Ageing

Replicative senescence of human cells in primary culture is a widely accepted model for studying the molecular mechanisms of human ageing. The standard model used for studying human ageing consists of fibroblasts explanted from the skin and grown intoin vitrosenescence. From this model, we have learned much about molecular mechanisms underlying the human ageing process; however, the model presents clear limitations. In particular, a long-standing dogma holds that replicative senescence involves resistance to apoptosis, a belief that has led to considerable confusion concerning the role of apoptosis during human ageing. While there are data suggesting that apoptotic cell death plays a key role for ageingin vitroand in the pathogenesis of various age-associated diseases, this is not reflected in the current literature onin vitrosenescence. In this article, I summarize key findings concerning the relationship between apoptosis and ageingin vivoand also review the literature concerning the role of apoptosis during in vitro senescence. Recent experimental findings, summarized in this article, suggest that apoptotic cell death (and probably other forms of cell death) are important features of the ageing process that can also be recapitulated in tissue culture systems to some extent. Another important lesson to learn from these studies is that mechanisms ofin vivosenescence differ considerably between various histotypes.

scholarly journals Opportunities for Ferroptosis in Cancer Therapy

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 986
Author(s):  
Kenji M. Fujihara ◽  
Bonnie Z. Zhang ◽  
Nicholas J. Clemons
Keyword(s):  
Lipid Peroxidation ◽  
Cell Death ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Therapeutic Strategy ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Cancer Therapeutics ◽  
Therapeutic Window ◽  
Anti Cancer

A critical hallmark of cancer cells is their ability to evade programmed apoptotic cell death. Consequently, resistance to anti-cancer therapeutics is a hurdle often observed in the clinic. Ferroptosis, a non-apoptotic form of cell death distinguished by toxic lipid peroxidation and iron accumulation, has garnered substantial attention as an alternative therapeutic strategy to selectively destroy tumours. Although there is a plethora of research outlining the molecular mechanisms of ferroptosis, these findings are yet to be translated into clinical compounds inducing ferroptosis. In this perspective, we elaborate on how ferroptosis can be leveraged in the clinic. We discuss a therapeutic window for compounds inducing ferroptosis, the subset of tumour types that are most sensitive to ferroptosis, conventional therapeutics that induce ferroptosis, and potential strategies for lowering the threshold for ferroptosis.

scholarly journals Caspase-Independent Regulated Necrosis Pathways as Potential Targets in Cancer Management

2021 ◽  
Vol 10 ◽  
Author(s):  
Jianyao Lou ◽  
Yunxiang Zhou ◽  
Zengyu Feng ◽  
Mindi Ma ◽  
Yihan Yao ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Multiple Modes ◽  
Cancer Management ◽  
Regulated Necrosis ◽  
Anti Cancer ◽  
Cancer Initiation

Regulated necrosis is an emerging type of cell death independent of caspase. Recently, with increasing findings of regulated necrosis in the field of biochemistry and genetics, the underlying molecular mechanisms and signaling pathways of regulated necrosis are gradually understood. Nowadays, there are several modes of regulated necrosis that are tightly related to cancer initiation and development, including necroptosis, ferroptosis, parthanatos, pyroptosis, and so on. What’s more, accumulating evidence shows that various compounds can exhibit the anti-cancer effect via inducing regulated necrosis in cancer cells, which indicates that caspase-independent regulated necrosis pathways are potential targets in cancer management. In this review, we expand the molecular mechanisms as well as signaling pathways of multiple modes of regulated necrosis. We also elaborate on the roles they play in tumorigenesis and discuss how each of the regulated necrosis pathways could be therapeutically targeted.

scholarly journals Apoptotic and Non-Apoptotic Modalities of Thymoquinone-Induced Lymphoma Cell Death: Highlight of the Role of Cytosolic Calcium and Necroptosis

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3579
Author(s):  
Mimoune Berehab ◽  
Redouane Rouas ◽  
Haidar Akl ◽  
Hugues Duvillier ◽  
Fabrice Journe ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Lines ◽  
Apoptotic Cell ◽  
Critical Role ◽  
B Cell Lymphoma ◽  
Cytosolic Calcium ◽  
Store Operated Calcium Entry ◽  
Safe Mechanism ◽  
Apoptotic Pathways

Targeting non-apoptotic modalities might be therapeutically promising in diffuse large B cell lymphoma (DLBCL) patients with compromised apoptotic pathways. Thymoquinone (TQ) has been reported to promote apoptosis in cancer cells, but little is known about its effect on non-apoptotic pathways. This work investigates TQ selectivity against DLBCL cell lines and the cell death mechanisms. TQ reduces cell viability and kills cell lines with minimal toxicity on normal hematological cells. Mechanistically, TQ promotes the mitochondrial caspase pathway and increases genotoxicity. However, insensitivity of most cell lines to caspase inhibition by z-VAD-fmk (benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone) pointed to a critical role of non-apoptotic signaling. In cells dying through non-apoptotic death, TQ increases endoplasmic reticulum (ER) stress markers and substantially increases cytosolic calcium ([Ca2+]c) through ER calcium depletion and activation of store-operated calcium entry (SOCE). Chelation of [Ca2+]c, but not SOCE inhibitors, reduces TQ-induced non-apoptotic cell death, highlighting the critical role of calcium in a non-apoptotic effect of TQ. Investigations showed that TQ-induced [Ca2+]c signaling is primarily initiated by necroptosis upstream to SOCE, and inhibition necroptosis by necrostatin-1 alone or with z-VAD-fmk blocks the cell death. Finally, TQ exhibits an improved selectivity profile over standard chemotherapy agents, suggesting a therapeutic relevance of the pro-necroptotic effect of TQ as a fail-safe mechanism for DLBCL therapies targeting apoptosis.

Biocatalytic synthesis of terpene esters and their biological activity in human glioma cells

2021 ◽  
Vol 22 ◽  
Author(s):  
Mateusz Kutyła ◽  
Aleksandra Maciejczyk ◽  
Mariusz Trytek ◽  
Joanna Jakubowicz-Gil
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Fold Increase ◽  
Point Of View ◽  
Terpene Alcohols ◽  
Human Glioblastoma Multiforme ◽  
Anti Cancer ◽  
Therapeutic Molecules ◽  
Resistance To Chemotherapy

Background: Gliomas are highly malignant brain tumors with high resistance to chemotherapy. Therefore, investigations of new therapeutic molecules with high anti-glioma activity are of great importance. Objective: In this work, biocatalytic esterification of terpene alcohols with proven anti-cancer activity was performed to enhance their potency to induce cell death in human glioblastoma multiforme T98G and anaplastic astrocytoma MOGGCCM cell lines in vitro. Method and Results: We used primary terpene alcohols and carboxylic acids with a length of two to nine carbon atoms. The structure of the drinks influenced the esterification efficiency, which decreased in the following order: monocyclic > linear > bicyclic. Terpene alcohols and their esters only induced apoptotic cell death, which is highly desirable from a therapeutic point of view but did not induce autophagy and necrosis. The esterification of perillyl alcohol with butyric acid caused a 4-fold increase in cell death induction in the T98G line. Citronellol valerate, caprylate, and pelargonate and myrtenol butyrate, caprylate, and pelargonate also showed higher activity than their alcohol precursors. Conclusion: We have herein shown that esterification of natural alcohols by biocatalysis can improve the activity for other compounds investigated for their anti-glioma activity.

Mixed-ligand copper(ii) Schiff base complexes: the vital role of co-ligands in DNA/protein interactions and cytotoxicity

2017 ◽  
Vol 41 (3) ◽  
pp. 1267-1283 ◽  
Author(s):  
Sellamuthu Kathiresan ◽  
Subramanian Mugesh ◽  
Jamespandi Annaraj ◽  
Maruthamuthu Murugan
Keyword(s):  
Cell Death ◽  
Cell Wall ◽  
Schiff Base ◽  
Protein Interactions ◽  
Apoptotic Cell ◽  
Vital Role ◽  
Mixed Ligand ◽  
Schiff Base Complexes ◽  
Antibacterial Mechanism

Four new mixed-ligand copper(ii) complexes display an antibacterial mechanism of cell death via cell-wall rupture and cytotoxicity via apoptotic cell death.

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