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Xylopine Induces Oxidative Stress and Causes G2M Phase Arrest, Triggering Caspase-Mediated Apoptosis by p53-Independent Pathway in HCT116 Cells
Joint Authors
Soares, Milena Botelho
Costa, Emmanoel V.
Bezerra, Daniel Pereira
Santos, Luciano de Souza
Silva, Valdenizia Rodrigues
Menezes, Leociley Rocha Alencar
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-12-06
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
Xylopine is an aporphine alkaloid that has cytotoxic activity to cancer cells.
In this study, the underlying mechanism of xylopine cytotoxicity was assessed in human colon carcinoma HCT116 cells.
Xylopine displayed potent cytotoxicity in different cancer cell lines in monolayer cultures and in a 3D model of cancer multicellular spheroids formed from HCT116 cells.
Typical morphology of apoptosis, cell cycle arrest in the G2/M phase, increased internucleosomal DNA fragmentation, loss of the mitochondrial transmembrane potential, and increased phosphatidylserine externalization and caspase-3 activation were observed in xylopine-treated HCT116 cells.
Moreover, pretreatment with a caspase-3 inhibitor (Z-DEVD-FMK), but not with a p53 inhibitor (cyclic pifithrin-α), reduced xylopine-induced apoptosis, indicating induction of caspase-mediated apoptosis by the p53-independent pathway.
Treatment with xylopine also caused an increase in the production of reactive oxygen/nitrogen species (ROS/RNS), including hydrogen peroxide and nitric oxide, but not superoxide anion, and reduced glutathione levels were decreased in xylopine-treated HCT116 cells.
Application of the antioxidant N-acetylcysteine reduced the ROS levels and xylopine-induced apoptosis, indicating activation of ROS-mediated apoptosis pathway.
In conclusion, xylopine has potent cytotoxicity to different cancer cell lines and is able to induce oxidative stress and G2/M phase arrest, triggering caspase-mediated apoptosis by the p53-independent pathway in HCT116 cells.
American Psychological Association (APA)
Santos, Luciano de Souza& Silva, Valdenizia Rodrigues& Menezes, Leociley Rocha Alencar& Soares, Milena Botelho& Costa, Emmanoel V.& Bezerra, Daniel Pereira. 2017. Xylopine Induces Oxidative Stress and Causes G2M Phase Arrest, Triggering Caspase-Mediated Apoptosis by p53-Independent Pathway in HCT116 Cells. Oxidative Medicine and Cellular Longevity،Vol. 2017, no. 2017, pp.1-13.
https://search.emarefa.net/detail/BIM-1195467
Modern Language Association (MLA)
Santos, Luciano de Souza…[et al.]. Xylopine Induces Oxidative Stress and Causes G2M Phase Arrest, Triggering Caspase-Mediated Apoptosis by p53-Independent Pathway in HCT116 Cells. Oxidative Medicine and Cellular Longevity No. 2017 (2017), pp.1-13.
https://search.emarefa.net/detail/BIM-1195467
American Medical Association (AMA)
Santos, Luciano de Souza& Silva, Valdenizia Rodrigues& Menezes, Leociley Rocha Alencar& Soares, Milena Botelho& Costa, Emmanoel V.& Bezerra, Daniel Pereira. Xylopine Induces Oxidative Stress and Causes G2M Phase Arrest, Triggering Caspase-Mediated Apoptosis by p53-Independent Pathway in HCT116 Cells. Oxidative Medicine and Cellular Longevity. 2017. Vol. 2017, no. 2017, pp.1-13.
https://search.emarefa.net/detail/BIM-1195467
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1195467