Alantolactone induces apoptosis in HepG2 cells through GSH depletion, inhibition of STAT3 activation, and mitochondrial dysfunction
Authors: Yongchen Zheng
Ting Li
Azhar Rasul
Tonghui Ma
Faisal Nawaz
Muhammad Khalil Ahmad Khan
Meiyan Sun
Muhammad Khan
Journal: BioMed Research International (2013)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: STAT3; apoptosis; alantolactone; GSH depletion; ROS generation
Affiliations: Central Research Laboratory, Jilin University Bethune Second Hospital, Changchun 130041, China., Central Research Laboratory, Jilin University Bethune Second Hospital, Changchun 130041, China, Department of Zoology, University of the Punjab, Quaid-e-Azam Campus, Lahore 54590, Pakistan, Key Laboratory of Inorganic Synthesis and Preparative Chemistry, Jilin University, Qianjin Street, Changchun 130012, China

Abstract:  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. 

Retracted: No

PubPeer comments:
 legend does not explain similiarities ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. , 
 Since pre-treatment of cells with NAC completely protected the cells from cytotoxic effects of alantolactone and even cells in both groups were morphologically similar, this might happened due to wrong labeling of microscopic images by mistake. The data is absolutely reproducible and authentic. We hope this mistake will not affect the findings of study. Moreover, we may provide new set of this figure as corrigendum , 
 Yes, I think a correction would be appropriate. With this type of confusion, how reliable is the quantification shown in (g)? *** Enhanced brightness ![file] ,