Apoptosis: mechanisms and relevance in cancer

  title={Apoptosis: mechanisms and relevance in cancer},
  author={Katrien Vermeulen and Dirk R. Van Bockstaele and Zwi N Berneman},
  journal={Annals of Hematology},
Apoptosis or programmed cell death is a process with typical morphological characteristics including plasma membrane blebbing, cell shrinkage, chromatin condensation and fragmentation. A family of cystein-dependent aspartate-directed proteases, called caspases, is responsible for the proteolytic cleavage of cellular proteins leading to the characteristic apoptotic features, e.g. cleavage of caspase-activated DNase resulting in internucleosomal DNA fragmentation. Currently, two pathways for… 

Apoptosis effector mechanisms: A requiem performed in different keys

The molecular regulation of caspases and various caspase-independent effectors of apoptosis are discussed, the potential context and/or limitations of these mechanisms are described, and why the understanding of these processes may have relevance in cancer where treatment is believed to engage apoptosis to destroy tumor cells.

Apoptosis signaling pathways and lymphocyte homeostasis

The understanding of the mechanisms that control the homeostasis of various lymphocyte populations, including caspase-independent pathways and granzyme-initiated pathways, are summarized.

Caspase-activated DNase (CAD)-independent oligonucleosomal DNA fragmentation in chronic myeloid leukaemia cells; a requirement for serine protease and Mn2+-dependent acidic endonuclease activity

It is shown that PBOX-6-induced oligonucleosomal DNA fragmentation occurs in the absence of caspase and CAD activation in CML cells and the existence of unidentified mitochondrial effectors of apoptosis is suggested.

Cell Death and Cancer, Novel Therapeutic Strategies

Besides its role in embryonic development, homeostasis maintenance and aging, apoptosis is also a defence mechanism by which infected, injured or mutated cells as a result of irradiation or chemotherapeutic drugs are eliminated.

Diepoxybutane activates the mitochondrial apoptotic pathway and mediates apoptosis in human lymphoblasts through oxidative stress.

Caspase-dependent Cleavage Disrupts the ERK Cascade Scaffolding Function of KSR1*♦

KSR1 undergoes caspase-dependent cleavage in apoptotic cells and that cleavage destroys the scaffolding function of the full-length KSR1 protein and generates a stable C-terminal fragment that can inhibit ERK activation, which is suggested to represent another mechanism whereby caspases down-regulate ERK survival signaling to promote cellular apoptosis.

Identification of DELE, a novel DAP3-binding protein which is crucial for death receptor-mediated apoptosis induction

It is shown that DELE actually binds to DAP3 in mammalian cells, and it is found that the cells stably expressing DELE are susceptible to apoptosis induction by the stimulation of TNF-α and TRAIL.

Induction of apoptosis by chelerythrine chloride through mitochondrial pathway and Bcl-2 family proteins in human hepatoma SMMC-7721 Cell

The results indicated that CHE may play an important role in suppression of tumor growth by inducing apoptosis in human hepatoma cells via the activation of a mitochondrial pathway and regulating the expression of Bcl-2 family proteins.

Etoposide Induces Protein Kinase Cδ- and Caspase-3-Dependent Apoptosis in Neuroblastoma Cancer Cells

Etoposide inhibits the proliferation of SK-N-AS neuroblastoma cancer cells and promotes protein kinase Cδ (PKCδ)- and caspase-dependent apoptosis and rottlerin blocks etoposide-induced apoptosis by inhibiting the PKCδ-mediated activation of caspasing-3 and by degrading caspases-2, which prevents casp enzyme-8 activation.

A Peptide-Based Target Screen Implicates the Protein Kinase CK2 in the Global Regulation of Caspase Signaling

A role for CK2-dependent phosphorylation as a global mechanism for inhibiting caspase signaling pathways is suggested, which may underlie its role in tumorigenesis.



Mammalian caspases: structure, activation, substrates, and functions during apoptosis.

This work has shown that apoptotic cell death is a genetically programmed, morphologically distinct form of cell death that can be triggered by a variety of physiological and pathological stimuli, and that proteases play critical roles in initiation and execution of this process.

Regulation of apoptosis by endoplasmic reticulum pathways

The potential underlying mechanisms involved in the regulation of the mitochondrial checkpoint are reviewed and pathways for ER–mitochondrial crosstalk pertinent to a number of cell death stimuli are discussed.

Cellular stress response and apoptosis in cancer therapy.

Understanding the complex interaction between different cellular programs provides insights into sensitivity or resistance of tumor cells and identifies molecular targets for rational therapeutic intervention strategies.

Mitochondria and apoptosis.

The possibility that the mechanism originally involved in the maintenance of the symbiosis between the bacterial ancestor of the mitochondria and the host cell precursor of eukaryotes provided the basis for the actual mechanism controlling cell survival is discussed.

Organelle-specific initiation of cell death pathways

Intriguingly, most organelle-specific death responses finally lead to either MMP or caspase activation, both of which might function as central integrators of the death pathway, thereby streamlining lysosome-, Golgi- or ER-elicited responses into a common pathway.

Caspase-dependent Cleavage of Signaling Proteins during Apoptosis

Results indicate that caspase-dependent cleavage of specific proteins induces the turn off of survival pathways, such as the extracellular signal-regulated kinase and phosphatidylinositol-3 kinase/Akt pathways, that could otherwise interfere with the apoptotic response.

Modulation of cell death by Bcl-XL through caspase interaction.

  • R. J. ClemE. Cheng J. Hardwick
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1998
Findings indicate that the recognition/cleavage site of Bcl-XL may facilitate protection against cell death by acting at the level of caspase activation and that cleavage of BCl-XL during the execution phase of cell death converts B cl-XL from a protective to a lethal protein.

BCL-2 family members and the mitochondria in apoptosis.

As the BCL-2 family members reside upstream of irreversible cellular damage and focus much of their efforts at the level of mitochondria, they play a pivotal role in deciding whether a cell will live or die, and it is argued that the amphipathic a-helical BH3 domain serves as a critical death domain in the pro-apoptotic members.

Mitochondrial Release of Caspase-2 and -9 during the Apoptotic Process

The data suggest that caspase-2 and -9 zymogens are essentially localized in mitochondria and that the disruption of the outer mitochondrial membrane occurring early during apoptosis may be critical for their subcellular redistribution and activation.