ReferenceID 6285
Induction of an MLKL mediated non-canonical necroptosis through reactive oxygen species by tanshinol A in lung cancer cells
Biochem Pharmacol
Recent discoveries revealed several types of programmed necrosis, such as necroptosis, ferroptosis, pyroptosis, etc. Necroptosis is mediated by signaling complexes with receptor-interacting protein kinases (RIPs) and mix
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Record Fields
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- Reference Id
- 6285
- Evidence Id
- 22875
- Core Evidence Id
- 22875
- Source Reference Id
- 5847
- Herb2 Reference Id
- HBREF006644
- Subject Paper Key
- HBIN045500_31678492
- Pubmed Id
- 31678492
- Doi
- 10.1016/j.bcp.2019.113684
- Paper Title
- Induction of an MLKL mediated non-canonical necroptosis through reactive oxygen species by tanshinol A in lung cancer cells
- Paper Abstract
- Recent discoveries revealed several types of programmed necrosis, such as necroptosis, ferroptosis, pyroptosis, etc. Necroptosis is mediated by signaling complexes with receptor-interacting protein kinases (RIPs) and mixed lineage kinase domain-like protein (MLKL). Here, we described an MLKL mediated non-canonical necroptosis through reactive oxygen species (ROS) in lung cancer cells triggered by a natural compound, tanshinol A (TSA). Morphologically, TSA-induced necrotic cell death is characterized by increased cell volume, transparent of cytoplasm, and rupture of the cell membrane. Biochemically, it induces intracellular ATP depletion and PI penetration. Molecularly, TSA-induced cell death is mediated by MLKL but independent of RIP1 and RIP3. Furthermore, TSA induces MLKL phosphorylation and membrane translocation, and cytosolic calcium accumulation. However, calcium shows no effect on TSA-induced cell death. Especially, TSA induces intracellular ROS generation, which was found to be the upstream of MLKL. Collectively, our data indicated that TSA triggers a novel type of programmed necrosis mediated by MLKL in lung cancer cells, which might have therapeutic potentials for lung cancer treatment.
- Journal
- Biochem Pharmacol
- Publish Year
- 2020
- Experiment Subject
- Experiment Type
- Cell Experiment
- Phenotype Related
- Ferroptosis; Lung Cancer; Programmed Necrosis; Pyroptosis; Necroptosis
- Paper Title Cn
- Paper Title En
- Induction of an MLKL mediated non-canonical necroptosis through reactive oxygen species by tanshinol A in lung cancer cells
- Bilingual Status
- semi_complete