Emerging Concepts in Cell Death [Oct 28, 2025] DOJINDO LABORATORIES

Cell death, once thought to follow distinct and irreversible routes, is now understood to involve overlapping and even reversible processes. Recent studies reveal new dimensions of how cells coordinate or recover from death signals, expanding the concept of programmed cell death. One study defines PANoptosis, a coordinated form of cell death in which apoptosis, pyroptosis, and necroptosis act together through the PANoptosome, linking inflammation and immune regulation in cancer. Another reports an NF-κB–dependent programmed cell revival after sublethal exposure to cell death–inducing agents, adding a reversible layer to cell-fate control.

PANoptosis in cancer: bridging molecular mechanisms to therapeutic innovations (Cell Mol Immunol., 2025) Review Article

Summary: PANoptosis is a newly characterized form of programmed cell death in which apoptosis, pyroptosis, and necroptosis operate together through the assembly of an inducible multiprotein scaffold known as the PANoptosome. This review focuses on cancer, describing the interplay among these death pathways and highlighting the defining characteristics and assembly mechanisms of PANoptosis. It also discusses functional roles in tumor initiation and progression, and its link to immune responses within the tumor microenvironment. Furthermore, the review explores the therapeutic implications of PANoptosis, including the potential of targeting this pathway in cancer therapy.

Programmed cell revival from imminent cell death enhances tissue repair and regeneration (EMBO J., 2025)

Summary: This study reveals that exposure to the cell death-inducing agent (LLOMe) triggers a previously unrecognized programmed cell regeneration, where cells avoid death, open chromatin, activate developmental and inflammatory genes, and rebuild to restore tissue repair. NF-κB is essential, defining a conserved self-healing pathway and a promising therapeutic target for regenerative medicine.

Highlighted technique: This study used flow cytometry and live cell confocal imaging to monitor cellular dynamics during the transition from death to recovery. Annexin V/PI staining, mitochondrial membrane potential (JC-1), lysosomal probe, and organelle markers such as TOM20 and Rab7 were used to monitor cell state and organelle integrity.

Cell Death Indicators (click to open/close)

Target	Kit & Probes
Apoptosis detection in multiple samples	Annexin V Apoptosis Plate Assay Kit
Ferroptosis: Ferrous ion (Fe²⁺)	FerroOrange(Intracellular), Mito-FerroGreen(Mitochondrial)
Ferroptosis: Lipid peroxide	Liperfluo(Intracellular), MitoPeDPP(Mitochondrial)
Ferroptosis: Lipid Peroxidation	Lipid Peroxidation Probe -BDP 581/591 C11-
Total ROS detection	Highly sensitive DCFH-DA or Photo-oxidation Resistant DCFH-DA
Mitochondrial membrane potential detection	JC-1 MitoMP Detection Kit, MT-1 MitoMP Detection Kit
Mitochondrial superoxide detection	MitoBright ROS Deep Red - Mitochondrial Superoxide Detection
Extracellular ATP measurement	Extracellular ATP Assay Kit-Luminescence
Cell proliferation/ cytotoxicity assay	Cell Counting Kit-8 and Cytotoxicity LDH Assay Kit-WST

Application Note (click to open/close)
> Changes in various indicators of cell death induced by drugs

	HepG2 cells treated with the apoptosis-inducing agent staurosporine or the ferroptosis-inducing agents Erastin and RSL3. After treatment, extracellular LDH, phosphatidylserine, cell viability, intracellular Fe²⁺ and lipid peroxidation were determined. The results showed that apoptosis-induced cells treated with staurosporine showed an increase in phosphatidylserine, a decrease in cell viability and an increase in extracellular LDH, indicating that cell death had occurred. On the other hand, intracellular Fe²⁺, an indicator of ferroptosis, remained unchanged. In cells treated with Erastin, a ferroptosis inducer, intracellular Fe²⁺ increased and cell viability decreased, but extracellular LDH and lipid peroxidation (lipid peroxidation: decrease in red fluorescence and increase in green fluorescence) did not increase. In cells in which ferroptosis was more strongly induced by co-treatment with RSL3 in addition to Erastin, increased intracellular Fe²⁺ and lipid peroxidation were observed. Moreover, decreased cell viability and increased dead cells were detected. Meanwhile, phosphatidylserine showed a lower rate of increase during ferroptosis induction compared to apoptosis-induced cells. These results suggest that cell death can be distinguished by evaluating a combination of cell death indicators.