Related Experiment Video

Updated: Jan 21, 2026

Analysis of Apoptosis in Zebrafish Embryos by Whole-mount Immunofluorescence to Detect Activated Caspase 3
08:20

Analysis of Apoptosis in Zebrafish Embryos by Whole-mount Immunofluorescence to Detect Activated Caspase 3

Published on: December 20, 2013

20.6K

Caspase-3-mediated GSDME activation contributes to cisplatin- and doxorubicin-induced secondary necrosis in mouse

Feng-Yi Mai1, Pengyan He2, Jie-Zhou Ye1

  • 1Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou, China.

Cell Proliferation
|July 27, 2019
PubMed
Abstract

Insights

Chemotherapy drugs like cisplatin and doxorubicin cause cell death in macrophages by activating caspase-3 and gasdermin E (GSDME), leading to secondary necrosis.

Area of Science:

  • Immunology
  • Cell Biology
  • Pharmacology

Background:

  • Chemotherapeutic agents induce cell death, involving mechanisms like secondary necrosis and pyroptosis.
  • Gasdermin E (GSDME) is a key mediator in these cell death pathways.
  • Understanding drug-induced macrophage toxicity is crucial for cancer therapy.

Purpose of the Study:

  • To investigate the role of GSDME in mediating the cytotoxic effects of cisplatin and doxorubicin on mouse macrophages.
  • To elucidate the specific cell death pathways involved in chemotherapy-induced macrophage death.

Main Methods:

  • Treatment of RAW 264.7 cells and bone marrow-derived macrophages (BMDMs) with cisplatin or doxorubicin.
  • Assay of necrosis using propidium iodide staining and protein expression via immunoblotting.
  • GSDME knockdown using small interfering RNA and in vivo evaluation of macrophage toxicity in mice.

Main Results:

  • Cisplatin and doxorubicin induced dose-dependent necrosis in macrophages.
  • Caspase-3 activation led to GSDME cleavage and subsequent secondary necrosis/pyroptosis.
  • GSDME knockdown and caspase-3 inhibition significantly reduced macrophage necrosis.
  • Cisplatin treatment depleted peritoneal macrophages in mice, correlating with GSDME activation.

Conclusions:

  • Chemotherapy-induced macrophage cytotoxicity is partly mediated by caspase-3/GSDME-dependent secondary necrosis.
  • GSDME plays a critical role in the toxic effects of cisplatin and doxorubicin on macrophages.
Keywords:
caspase-3chemotherapeutic drugsgasdermin Emacrophagessecondary necrosis

More Related Videos

Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages08:41

Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages

Published on: April 6, 2022

3.1K
Caspase-3 Activity in the Rat Amygdala Measured by Spectrofluorometry After Myocardial Infarction08:41

Caspase-3 Activity in the Rat Amygdala Measured by Spectrofluorometry After Myocardial Infarction

Published on: January 12, 2016

12.3K

Related Concept Videos

Secondary Active Transport01:55

Secondary Active Transport

One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme “pump” embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...
137.3K
Secondary Active Transport01:32

Secondary Active Transport

One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme "pump" embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...
9.4K
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...
6.4K
Primary and Secondary Growth in Roots and Shoots03:02

Primary and Secondary Growth in Roots and Shoots

Vascular plants, which account for over 90% of the Earth’s vegetation, all undergo primary growth—which lengthens roots and shoots. Many land plants, notably woody plants, also undergo secondary growth—which thickens roots and shoots.
60.2K
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...
13.8K
ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH301:11

ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH3

All ortho–para directors, excluding halogens, are activating groups. These groups donate electrons to the ring, making the ring carbons electron-rich. Consequently, the reactivity of the aromatic ring towards electrophilic substitution increases. For instance, the nitration of anisole is about 10,000 times faster than the nitration of benzene. The electron-donating effect of the methoxy group in anisole activates the ortho and para positions on the ring and stabilizes the corresponding...
7.3K