Related Experiment Video

Updated: Aug 8, 2026

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

Imexon-induced apoptosis in multiple myeloma tumor cells is caspase-8 dependent

Andrew M Evens1, Sheila Prachand, Bo Shi

  • 1Departments of Medicine and Pathology, Feinberg School of Medicine and the Robert H Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois 60611, USA.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|February 24, 2004
PubMed

Insights

Imexon demonstrates broad antimyeloma activity by inducing apoptosis, independent of reactive oxygen species (ROS) production. This cytotoxicity mechanism is caspase-8 dependent in both sensitive and resistant myeloma cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Imexon, a 2-cyanoaziridine agent, previously showed efficacy against chemotherapy-sensitive myeloma cells.
  • Its mechanism involved apoptosis, reduced glutathione, and increased reactive oxygen species (ROS).

Purpose of the Study:

  • To investigate the mechanism of imexon cytotoxicity in various myeloma cell lines.
  • To assess imexon's efficacy against dexamethasone- and chemotherapy-resistant myeloma cells.

Main Methods:

  • Cytotoxicity, apoptosis, and redox state were examined in sensitive and resistant myeloma cell lines.
  • Caspase-3 and caspase-8 activity, Bcl-2:bax ratio, glutathione levels, and ROS production were analyzed.

Main Results:

  • Imexon exhibited time- and dose-dependent cytotoxicity across all tested myeloma cell lines.
  • Apoptosis, marked by cleaved caspase-3, was the primary mechanism of imexon-induced cell death.
  • Caspase-8-dependent apoptosis was observed in specific cell lines.
  • Glutathione depletion and ROS generation occurred only at high imexon concentrations in certain cell lines, without significant DNA damage.

Conclusions:

  • Imexon possesses broad antimyeloma activity mediated by apoptosis.
  • The cytotoxic effect is not dependent on ROS production.
  • A caspase-8-dependent mechanism contributes to imexon's cytotoxicity in dexamethasone-sensitive and -resistant myeloma cells.
Abstract

More Related Videos

Real Time Detection of In Vitro Tumor Cell Apoptosis Induced by CD8+ T Cells to Study Immune Suppressive Functions of Tumor-infiltrating Myeloid Cells09:57

Real Time Detection of In Vitro Tumor Cell Apoptosis Induced by CD8+ T Cells to Study Immune Suppressive Functions of Tumor-infiltrating Myeloid Cells

Published on: January 29, 2019

Evaluation of Caspase Activation to Assess Innate Immune Cell Death10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

Related Concept Videos

Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
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.
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.
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...
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...