Alantolactone Induces Apoptosis in HepG2 Cells through GSH Depletion, Inhibition of STAT3 Activation, and Mitochondrial Dysfunction
Joint Authors
Rasul, Azhar
Khan, Muhammad
Ma, Tonghui
Li, Ting
Ahmad Khan, Muhammad Khalil
Nawaz, Faisal
Zheng, Yongchen
Sun, Meiyan
Source
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-12-27
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
Signal transducer and activator of transcription 3 (STAT3) constitutively expresses in human liver cancer cells and has been implicated in apoptosis resistance and tumorigenesis.
Alantolactone, a sesquiterpene lactone, has been shown to possess anticancer activities in various cancer cell lines.
In our previous report, we showed that alantolactone induced apoptosis in U87 glioblastoma cells via GSH depletion and ROS generation.
However, the molecular mechanism of GSH depletion remained unexplored.
The present study was conducted to envisage the molecular mechanism of alantolactone-induced apoptosis in HepG2 cells by focusing on the molecular mechanism of GSH depletion and its effect on STAT3 activation.
We found that alantolactone induced apoptosis in HepG2 cells in a dose-dependent manner.
This alantolactone-induced apoptosis was found to be associated with GSH depletion, inhibition of STAT3 activation, ROS generation, mitochondrial transmembrane potential dissipation, and increased Bax/Bcl-2 ratio and caspase-3 activation.
This alantolactone-induced apoptosis and GSH depletion were effectively inhibited or abrogated by a thiol antioxidant, N-acetyl-L-cysteine (NAC).
The data demonstrate clearly that intracellular GSH plays a central role in alantolactone-induced apoptosis in HepG2 cells.
Thus, alantolactone may become a lead chemotherapeutic candidate for the treatment of liver cancer.
American Psychological Association (APA)
Khan, Muhammad& Li, Ting& Ahmad Khan, Muhammad Khalil& Rasul, Azhar& Nawaz, Faisal& Sun, Meiyan…[et al.]. 2012. Alantolactone Induces Apoptosis in HepG2 Cells through GSH Depletion, Inhibition of STAT3 Activation, and Mitochondrial Dysfunction. BioMed Research International،Vol. 2013, no. 2013, pp.1-11.
https://search.emarefa.net/detail/BIM-1030834
Modern Language Association (MLA)
Khan, Muhammad…[et al.]. Alantolactone Induces Apoptosis in HepG2 Cells through GSH Depletion, Inhibition of STAT3 Activation, and Mitochondrial Dysfunction. BioMed Research International No. 2013 (2013), pp.1-11.
https://search.emarefa.net/detail/BIM-1030834
American Medical Association (AMA)
Khan, Muhammad& Li, Ting& Ahmad Khan, Muhammad Khalil& Rasul, Azhar& Nawaz, Faisal& Sun, Meiyan…[et al.]. Alantolactone Induces Apoptosis in HepG2 Cells through GSH Depletion, Inhibition of STAT3 Activation, and Mitochondrial Dysfunction. BioMed Research International. 2012. Vol. 2013, no. 2013, pp.1-11.
https://search.emarefa.net/detail/BIM-1030834
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1030834