Cisplatin cytotoxicity: DNA and plasma membrane targets

Related Experiment Video

Updated: Jun 28, 2026

A High-Throughput Comet Assay Approach for Assessing Cellular DNA Damage
07:57

A High-Throughput Comet Assay Approach for Assessing Cellular DNA Damage

Published on: May 10, 2022

Amélie Rebillard1, Dominique Lagadic-Gossmann, Marie-Thérèse Dimanche-Boitrel

  • 1INSERM UMR 620, IFR 140 GFAS, and University of Rennes 1, Rennes, France. amelie.rebillard@uhb.fr

Current Medicinal Chemistry
|November 11, 2008
PubMed

Insights

Cisplatin triggers cancer cell death via plasma membrane changes, not just DNA damage. This review explores how membrane fluidity, NHE1 inhibition, and acid sphingomyelinase activation impact the Fas pathway in cisplatin-induced apoptosis.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Apoptosis is a key mechanism in cancer therapy, but its pathways are not fully understood.
  • DNA-damaging agents often induce apoptosis via mitochondrial pathways, but some, like cisplatin, utilize plasma membrane disruption.
  • The Fas death receptor pathway is implicated in cisplatin-induced apoptosis.

Purpose of the Study:

  • To review the early plasma membrane events involved in cisplatin-induced apoptosis.
  • To highlight the role of plasma membrane alterations in triggering the Fas death pathway.

Main Methods:

  • Literature review focusing on biochemical and cellular mechanisms.
  • Analysis of studies investigating plasma membrane properties and signaling pathways.

Main Results:

  • Cisplatin induces apoptosis through mechanisms involving plasma membrane disruption.
  • Key early events include altered plasma membrane fluidity, inhibition of the NHE1 exchanger, and activation of acid sphingomyelinase.
  • These events are linked to the activation of the Fas death pathway.

Conclusions:

  • Early plasma membrane events are critical in cisplatin-induced apoptosis.
  • Understanding these membrane-associated pathways can offer new therapeutic strategies for cancer treatment.

Related Concept Videos

DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
Inhibitors of Bacterial DNA Synthesis01:28

Inhibitors of Bacterial DNA Synthesis

Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively...