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Enhancement of Quercetin-Induced Apoptosis by Cotreatment with Autophagy Inhibitor Is Associated with Augmentation of BAK-Dependent Mitochondrial Pathway in Jurkat T Cells
Joint Authors
Ha, Eun Ji
Kim, Ki Yun
Kim, Chae Eun
Jun, Do Youn
Kim, Young Kyoo
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-16, 16 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-11-15
Country of Publication
Egypt
No. of Pages
16
Main Subjects
Abstract EN
A flavonoid antioxidant quercetin promotes dose-dependent activation of the ATM-CHK-p53 pathway, downregulation of antiapoptotic survivin, and upregulation of proapoptotic NOXA in human T cell acute lymphoblastic leukemia Jurkat clones (J/Neo and J/BCL-XL).
However, the downregulation of antiapoptotic BAG3 and MCL-1 occurred in J/Neo cells but not in J/BCL-XL cells overexpressing BCL-XL.
Additionally, several BCL-XL-sensitive intrinsic mitochondrial apoptotic events including apoptotic sub-G1 cell accumulation, TUNEL-positive DNA fragmentation, BAK activation, mitochondrial membrane potential (Δψm) loss, caspase-9/caspase-8/caspase-3 activation, and PARP cleavage were induced only in J/Neo cells.
Both cytosolic and mitochondrial ROS levels were elevated in quercetin-treated J/Neo cells; however, the ROS elevations were almost completely abrogated in J/BCL-XL cells, suggesting the ROS elevations were downstream of BCL-XL-sensitive mitochondrial damage and dysfunction.
Wild-type A3, FADD-deficient I2.1, and caspase-8-deficient I9.2 Jurkat clones exhibited similar susceptibilities to the cytotoxicity of quercetin, excluding an involvement of extrinsic pathway in triggering the apoptosis.
The autophagic events such as attenuation of AKT-mTOR pathway, formation of acridine orange-stainable acidic vesicular organelles, conversion of microtubule-associated protein 1 light chain 3-I (LC3-I) to LC3-II, and downregulation of p62/SQSTM1 level were detected in quercetin-treated J/Neo and J/BCL-XL cells, regardless of BCL-XL overexpression.
Cotreatment with the autophagy inhibitor (3-methyladenine, LY294002, or chloroquine) resulted in a significant enhancement of quercetin-induced BAK activation and subsequently the mitochondrial damage-mediated apoptosis pathway by augmenting the downregulation of BAG3 and MCL-1 levels in J/Neo cells.
These results demonstrated that quercetin induces intrinsic apoptosis and cytoprotective autophagy, and autophagy inhibition can potentiate BAK-dependent apoptotic activity of quercetin in Jurkat T cells.
American Psychological Association (APA)
Ha, Eun Ji& Kim, Ki Yun& Kim, Chae Eun& Jun, Do Youn& Kim, Young Kyoo. 2019. Enhancement of Quercetin-Induced Apoptosis by Cotreatment with Autophagy Inhibitor Is Associated with Augmentation of BAK-Dependent Mitochondrial Pathway in Jurkat T Cells. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-16.
https://search.emarefa.net/detail/BIM-1205393
Modern Language Association (MLA)
Ha, Eun Ji…[et al.]. Enhancement of Quercetin-Induced Apoptosis by Cotreatment with Autophagy Inhibitor Is Associated with Augmentation of BAK-Dependent Mitochondrial Pathway in Jurkat T Cells. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-16.
https://search.emarefa.net/detail/BIM-1205393
American Medical Association (AMA)
Ha, Eun Ji& Kim, Ki Yun& Kim, Chae Eun& Jun, Do Youn& Kim, Young Kyoo. Enhancement of Quercetin-Induced Apoptosis by Cotreatment with Autophagy Inhibitor Is Associated with Augmentation of BAK-Dependent Mitochondrial Pathway in Jurkat T Cells. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-16.
https://search.emarefa.net/detail/BIM-1205393
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1205393