Related Experiment Video

Updated: Jun 1, 2026

Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons
10:36

Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons

Published on: November 6, 2017

Salinomycin induces calpain and cytochrome c-mediated neuronal cell death

W Boehmerle1, M Endres

  • 1Department of Neurology, Charite-Universitätsmedizin Berlin, Berlin, Germany. wolfgang.boehmerle@charite.de

Cell Death & Disease
|June 3, 2011
PubMed

Insights

Salinomycin effectively eliminates cancer stem cells but causes neurotoxicity. This study reveals that elevated sodium and calcium levels trigger apoptosis in nerve cells, offering insights for preventing salinomycin

Area of Science:

  • Pharmacology
  • Neuroscience
  • Cancer Biology

Background:

  • Salinomycin, an ionophore antibiotic, shows promise in eliminating cancer stem cells (CSCs).
  • A significant limitation to its clinical use is its neurotoxicity and muscular toxicity.

Purpose of the Study:

  • To elucidate the mechanisms underlying salinomycin-induced neurotoxicity.
  • To identify potential targets for mitigating these adverse effects.

Main Methods:

  • Investigated the effects of salinomycin on dorsal root ganglia and Schwann cells in vitro.
  • Utilized ion measurements, calcium imaging, and apoptosis assays.
  • Examined the role of Na+/Ca2+ exchangers (NCXs) and caspase activation.

Main Results:

  • Salinomycin induces neurotoxicity by increasing cytosolic Na+, leading to Ca2+ overload via NCXs.
  • This Ca2+ dysregulation activates calpain and caspase-dependent apoptosis.
  • Inhibition of calpain and mitochondrial NCXs significantly reduced salinomycin's cytotoxicity.

Conclusions:

  • Salinomycin's neurotoxicity is mediated by Na+- and Ca2+-dependent apoptotic pathways.
  • Targeting calpain and mitochondrial NCXs may prevent salinomycin-induced peripheral neuropathy.
  • Findings provide a basis for developing strategies to manage salinomycin's side effects.

More Related Videos

Monitoring Cleaved Caspase-3 Activity and Apoptosis of Immortalized Oligodendroglial Cells using Live-cell Imaging and Cleaveable Fluorogenic-dye Substrates Following Potassium-induced Membrane Depolarization10:45

Monitoring Cleaved Caspase-3 Activity and Apoptosis of Immortalized Oligodendroglial Cells using Live-cell Imaging and Cleaveable Fluorogenic-dye Substrates Following Potassium-induced Membrane Depolarization

Published on: January 13, 2012

Related Concept Videos

Cellular Injury IV: Necrosis01:16

Cellular Injury IV: Necrosis

Necrosis is a form of irreversible cell death caused by severe injury such as ischemia, toxins, or trauma. Unlike programmed cell death, it is an uncontrolled, pathological process that typically provokes inflammation in surrounding tissues.Pathophysiologic ChangesNecrosis begins when cells sustain critical damage, leading to swelling of organelles, particularly mitochondria, and rapid ATP depletion. As energy levels decline, membrane ion pumps fail, leading to calcium influx and eventually,...
Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...
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...
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
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...
Cellular Injury IlI: Cellular Death01:11

Cellular Injury IlI: Cellular Death

Cell death is the irreversible loss of cellular structure and function, representing the final stage of severe injury. It plays a key role in both normal physiology and disease.Types of Cell DeathThe two main types are necrosis and apoptosis, though others like necroptosis and pyroptosis also exist.Necrosis:Necrosis is an unregulated form of cell death caused by severe injury such as trauma, toxins, or ischemia. It is characterized by cell swelling, membrane loss, rupture, and leakage of...