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Pristimerin Exacerbates Cellular Injury in Conditionally Reprogrammed Patient-Derived Lung Adenocarcinoma Cells by Aggravating Mitochondrial Impairment and Endoplasmic Reticulum Stress through EphB4CDC42N-WASP Signaling
Joint Authors
Lei, Yiyan
Tang, Yubo
Huang, Shuai
Li, Zhangyan
Chen, Xiangtian
Luo, Honghe
Cheng, Chao
Chen, Jie
Chen, Xiao
Zou, Xuenong
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-25, 25 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-07-11
Country of Publication
Egypt
No. of Pages
25
Main Subjects
Abstract EN
Lung cancer is the most common and lethal malignant disease for which the development of efficacious chemotherapeutic agents remains an urgent need.
Pristimerin (PRIS), a natural bioactive component isolated from various plant species in the Celastraceae and Hippocrateaceae families, has been reported to exhibit outstanding antitumor effects in several types of cells.
However, the underlying mechanisms involved remain poorly understood.
Here, we reported the novel finding that PRIS significantly suppressed lung cancer growth in conditionally reprogrammed patient-derived lung adenocarcinoma cells (CRLCs).
We demonstrated that PRIS inhibited the cell viabilities, migrative and invaded abilities, and capillary structure formation of CRLCs.
Furthermore, our results clarified that PRIS induced mitochondrial dysfunction through reactive oxygen species (ROS) generation, activation of caspase-9, caspase-3, and caspase-4, and expression of endoplasmic reticulum (ER) stress-associated proteins.
Inhibition of ER stress by 4-PBA (4-phenylbutyric acid, a specific ER stress inhibitor) or CHOP siRNA transfection ameliorated PRIS-induced loss of mitochondrial membrane potential and intrinsic apoptosis.
The present study also provides mechanistic evidence that PRIS suppressed the EphB4/CDC42/N-WASP signaling pathway, which is required for mitochondrial-mediated intrinsic apoptosis, activation of ER stress, and stimulation of caspase-4 induced by PRIS, and consequently resulting in suppressed cell viability, migration, and angiogenesis in CRLCs.
Taken together, by providing a mechanistic insight into the modulation of ER stress-induced cell death in CRLCs by PRIS, we suggest that PRIS has a strong potential of being a new antitumor therapeutic agent with applications in the fields of human lung adenocarcinoma.
American Psychological Association (APA)
Tang, Yubo& Lei, Yiyan& Huang, Shuai& Li, Zhangyan& Chen, Xiangtian& Luo, Honghe…[et al.]. 2020. Pristimerin Exacerbates Cellular Injury in Conditionally Reprogrammed Patient-Derived Lung Adenocarcinoma Cells by Aggravating Mitochondrial Impairment and Endoplasmic Reticulum Stress through EphB4CDC42N-WASP Signaling. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-25.
https://search.emarefa.net/detail/BIM-1205369
Modern Language Association (MLA)
Tang, Yubo…[et al.]. Pristimerin Exacerbates Cellular Injury in Conditionally Reprogrammed Patient-Derived Lung Adenocarcinoma Cells by Aggravating Mitochondrial Impairment and Endoplasmic Reticulum Stress through EphB4CDC42N-WASP Signaling. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-25.
https://search.emarefa.net/detail/BIM-1205369
American Medical Association (AMA)
Tang, Yubo& Lei, Yiyan& Huang, Shuai& Li, Zhangyan& Chen, Xiangtian& Luo, Honghe…[et al.]. Pristimerin Exacerbates Cellular Injury in Conditionally Reprogrammed Patient-Derived Lung Adenocarcinoma Cells by Aggravating Mitochondrial Impairment and Endoplasmic Reticulum Stress through EphB4CDC42N-WASP Signaling. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-25.
https://search.emarefa.net/detail/BIM-1205369
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1205369