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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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