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Alantolactone Induces Apoptosis in HepG2 Cells through GSH Depletion, Inhibition of STAT3 Activation, and Mitochondrial Dysfunction

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...

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Autores principales: Khan, Muhammad, Li, Ting, Ahmad Khan, Muhammad Khalil, Rasul, Azhar, Nawaz, Faisal, Sun, Meiyan, Zheng, Yongchen, Ma, Tonghui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3591150/
https://www.ncbi.nlm.nih.gov/pubmed/23533997
http://dx.doi.org/10.1155/2013/719858
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author Khan, Muhammad
Li, Ting
Ahmad Khan, Muhammad Khalil
Rasul, Azhar
Nawaz, Faisal
Sun, Meiyan
Zheng, Yongchen
Ma, Tonghui
author_facet Khan, Muhammad
Li, Ting
Ahmad Khan, Muhammad Khalil
Rasul, Azhar
Nawaz, Faisal
Sun, Meiyan
Zheng, Yongchen
Ma, Tonghui
author_sort Khan, Muhammad
collection PubMed
description 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.
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spelling pubmed-35911502013-03-26 Alantolactone Induces Apoptosis in HepG2 Cells through GSH Depletion, Inhibition of STAT3 Activation, and Mitochondrial Dysfunction Khan, Muhammad Li, Ting Ahmad Khan, Muhammad Khalil Rasul, Azhar Nawaz, Faisal Sun, Meiyan Zheng, Yongchen Ma, Tonghui Biomed Res Int Research Article 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. Hindawi Publishing Corporation 2013 2012-12-27 /pmc/articles/PMC3591150/ /pubmed/23533997 http://dx.doi.org/10.1155/2013/719858 Text en Copyright © 2013 Muhammad Khan et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Khan, Muhammad
Li, Ting
Ahmad Khan, Muhammad Khalil
Rasul, Azhar
Nawaz, Faisal
Sun, Meiyan
Zheng, Yongchen
Ma, Tonghui
Alantolactone Induces Apoptosis in HepG2 Cells through GSH Depletion, Inhibition of STAT3 Activation, and Mitochondrial Dysfunction
title Alantolactone Induces Apoptosis in HepG2 Cells through GSH Depletion, Inhibition of STAT3 Activation, and Mitochondrial Dysfunction
title_full Alantolactone Induces Apoptosis in HepG2 Cells through GSH Depletion, Inhibition of STAT3 Activation, and Mitochondrial Dysfunction
title_fullStr Alantolactone Induces Apoptosis in HepG2 Cells through GSH Depletion, Inhibition of STAT3 Activation, and Mitochondrial Dysfunction
title_full_unstemmed Alantolactone Induces Apoptosis in HepG2 Cells through GSH Depletion, Inhibition of STAT3 Activation, and Mitochondrial Dysfunction
title_short Alantolactone Induces Apoptosis in HepG2 Cells through GSH Depletion, Inhibition of STAT3 Activation, and Mitochondrial Dysfunction
title_sort alantolactone induces apoptosis in hepg2 cells through gsh depletion, inhibition of stat3 activation, and mitochondrial dysfunction
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3591150/
https://www.ncbi.nlm.nih.gov/pubmed/23533997
http://dx.doi.org/10.1155/2013/719858
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