Honokiol induces caspase-independent paraptosis via reactive oxygen species production that is accompanied by apoptosis in leukemia cells |
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| Authors: | Yao Wang Xiuping Zhu Zehong Yang Xiaojun Zhao |
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| Institution: | 1. West China Hospital Laboratory of Nanomedicine and Institute for Nanobiomedical Technology and Membrane Biology, Sichuan University, Chengdu 610041, Sichuan, China;2. First Hospital of Xi’an, Shaanxi Provincial Key Lab of Ophthalmology, Shaanxi Institute of Ophthalmology, Xi’an 710002, Shaanxi, China;3. Center for Biomedical Engineering, NE47-379, Massachusetts Institute of Technology, Cambridge, MA 02139-4307, USA;1. Division of Nephrology, Children’s Hospital, Boston, MA, United States;2. Harvard Medical School, Boston, MA, United States;3. Department of Dermatology, Emory University School of Medicine, Winship Cancer Center, and Atlanta Veterans Administration Hospital, Atlanta, GA, United States;1. Vienna University of Technology, Institute of Applied Synthetic Chemistry, Getreidemarkt 9/163-OC, 1060 Vienna, Austria;2. Medical University of Vienna, Department of Molecular Neurosciences, Spitalgasse 4, 1090 Vienna, Austria;1. Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, People''s Republic of China;2. Department of Cardiology, The General Hospital of Benxi Iron and Steel Co. Ltd., The Fifth Affiliated Hospital of China Medical University, Benxi, Liaoning 117000, People''s Republic of China;1. Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China;2. Pharmacognosy Division, Medical College of Chinese People''s Armed Police Force, Tianjin 300162, PR China;3. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, PR China;4. Tianjin First Central Hospital, Tianjin 300192, PR China;1. Research Institute of Pesticidal Design & Synthesis, College of Sciences, Northwest A&F University, Yangling, 712100 Shaanxi Province, PR China;2. College of Plant Protection, Northwest A&F University, Yangling, 712100 Shaanxi Province, PR China;1. Department of Surgery, University of Kansas Medical Center, Kansas City, KS, USA;2. Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA;3. University of Kansas Cancer Center, 3901 Rainbow Blvd., Mail Stop 3040, Kansas City, KS 66160, USA |
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| Abstract: | Our previous report has shown that honokiol (HNK), a constituent of Magnolia officinalis, induces a novel form of non-apoptotic programmed cell death in human leukemia NB4 and K562 cells. In this study, we further explored the relationship between the cell death pathway and cytoplasmic vacuolization and studied the underlying mechanism of leukemia cell death mediated by honokiol. The results showed that low concentrations of honokiol activated an novel alternative cell death fitted the criteria of paraptosis, such as cytoplasmic vacuolization derived from endoplasmic reticulum swelling, lack of caspase activation, and lack of apoptotic morphology. Results further indicated that the cell death was time- and concentration-dependent. In addition, honokiol-induced paraptosis did not involve membrane blebbing, chromatin condensation and phosphatidylserine exposure at the outer of the plasma membrane. The mechanism of the cell death may be associated, at least in part, with the increased generation of reactive oxygen species. Further analysis showed that honokiol induces cell death predominantly via paraptosis and to a certain extent via apoptosis in NB4 cells, and predominantly via apoptosis and to a certain extent via paraptosis in K562 cells. These observations suggest that cell death occurs via more than one pathway in leukemia cells and targeting paraptosis may be an alternative and promising avenue for honokiol in leukemia therapy. |
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