Related Experiment Video

Updated: Aug 9, 2026

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

Cytosine arabinoside induces programmed endothelial cell death through the caspase-3 pathway

Ida M Ki Moore1, Carrie J Merkle, Petra Miketova

  • 1College of Nursing, University of Arizona, Tucson 85721-0203, USA. kmoore@nursing.arizona.edu

Biological Research for Nursing
|April 4, 2006
PubMed

Insights

Cytosine arabinoside (ARA-C) induces apoptosis in non-dividing endothelial cells, potentially explaining treatment toxicity. Hydrocortisone may offer protection by reducing caspase-3 activity.

Area of Science:

  • Cell Biology
  • Pharmacology
  • Toxicology

Background:

  • Cytosine arabinoside (ARA-C) is a known anti-cancer drug.
  • The effects of ARA-C on nonmalignant cells, particularly endothelial cells, are not well understood.
  • Understanding these effects is crucial for managing treatment-related toxicity.

Purpose of the Study:

  • To investigate the impact of ARA-C on quiescent vascular endothelial cells.
  • To assess ARA-C's effects on cell viability and apoptosis induction.
  • To determine if hydrocortisone can mitigate ARA-C-induced apoptosis via caspase-3 inhibition.

Main Methods:

  • Cultured human endothelial cells were treated with varying concentrations of ARA-C and hydrocortisone.
  • Cell viability was measured using MTS assays.
  • Apoptosis was quantified via Annexin-V staining and DNA fragmentation assays.
  • Caspase-3 activity was assessed using a fluorescence-based enzymatic assay.

Main Results:

  • ARA-C significantly decreased endothelial cell viability in a dose- and time-dependent manner.
  • Increased concentrations and duration of ARA-C treatment led to a higher percentage of apoptotic cells.
  • ARA-C exposure resulted in increased DNA fragmentation and caspase-3 activity.
  • Hydrocortisone treatment attenuated the increase in caspase-3 activity induced by ARA-C.

Conclusions:

  • Cytosine arabinoside induces apoptosis in non-dividing vascular endothelial cells.
  • Hydrocortisone may protect endothelial cells from ARA-C-induced apoptosis by suppressing caspase-3 activation.
  • These findings highlight potential mechanisms of ARA-C toxicity and protective strategies.

More Related Videos

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry05:29

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry

Published on: March 24, 2023

Related Concept Videos

The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...