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Induction of an MLKL mediated non-canonical necroptosis through reactive oxygen species by tanshinol A in lung cancer cells
Liu,Xin1; Zhang,Yiying1; Gao,Hongwei1; Hou,Ying1; Lu,Jin jian1; Feng,Yulin2; Xu,Qiongming3; Liu,Bo4; Chen,Xiuping1
2020
Source PublicationBiochemical Pharmacology
ISSN0006-2952
Volume171
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.

KeywordLung Cancer Mlkl Programmed Necrosis Ros Tanshinol a
DOI10.1016/j.bcp.2019.113684
URLView the original
Indexed BySCIE
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000519219000007
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Cited Times [WOS]:5   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorChen,Xiuping
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macau,Macau,China
2.State Key Laboratory of Innovative Drug and Efficient Energy-Saving Pharmaceutical Equipment,Jiangxi University of Traditional Chinese Medicine,Nanchang,330004,China
3.College of Pharmaceutical Science,Soochow University,Suzhou,215123,China
4.Key Laboratory of Green Chemistry & Technology of Ministry of Education,College of Chemistry,Sichuan University,Chengdu,610064,China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Liu,Xin,Zhang,Yiying,Gao,Hongwei,et al. Induction of an MLKL mediated non-canonical necroptosis through reactive oxygen species by tanshinol A in lung cancer cells[J]. Biochemical Pharmacology,2020,171.
APA Liu,Xin,Zhang,Yiying,Gao,Hongwei,Hou,Ying,Lu,Jin jian,Feng,Yulin,Xu,Qiongming,Liu,Bo,&Chen,Xiuping.(2020).Induction of an MLKL mediated non-canonical necroptosis through reactive oxygen species by tanshinol A in lung cancer cells.Biochemical Pharmacology,171.
MLA Liu,Xin,et al."Induction of an MLKL mediated non-canonical necroptosis through reactive oxygen species by tanshinol A in lung cancer cells".Biochemical Pharmacology 171(2020).
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