Abstract:
:Ferroptosis, a newly discovered form of cell death mediated by reactive oxygen species (ROS) and lipid peroxidation, has recently been shown to have an impact on various cancer types; however, so far there are only few studies about its role in hepatocellular carcinoma (HCC). The delicate equilibrium of ROS in cancer cells has found to be crucial for cell survival, thus increased levels may trigger ferroptosis in HCC. In our study, we investigated the effect of different ROS modulators and ferroptosis inducers on a human HCC cell line and a human hepatoblastoma cell line. We identified a novel synergistic cell death induction by the combination of Auranofin and buthionine sulfoxime (BSO) or by Erastin and BSO at subtoxic concentrations. We found a caspase-independent, redox-regulated cell death, which could be rescued by different inhibitors of ferroptosis. Both cotreatments stimulated lipid peroxidation. All these findings indicated ferroptotic cell death. Both cotreatments affected the canonical ferroptosis pathway through GPX4 downregulation. We also found an accumulation of Nrf2 and HO-1, indicating an additional effect on the non-canonical pathway. Our results implicate that targeting these two main ferroptotic pathways simultaneously can overcome chemotherapy resistance in HCC.
journal_name
Transl Oncoljournal_title
Translational oncologyauthors
Lippmann J,Petri K,Fulda S,Liese Jdoi
10.1016/j.tranon.2020.100785subject
Has Abstractpub_date
2020-08-01 00:00:00pages
100785issue
8issn
1936-5233pii
S1936-5233(20)30021-8journal_volume
13pub_type
杂志文章abstract:INTRODUCTION:An increase in detection of early-stage asymptomatic lung tumors could increase the overall survival rate of lung cancer patients. A new approach to cancer (pre-)screening focusses on detecting field cancerization instead of the tumor itself. The objective of this study was to investigate the use of optica...
journal_title:Translational oncology
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journal_title:Translational oncology
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journal_title:Translational oncology
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journal_title:Translational oncology
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journal_title:Translational oncology
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journal_title:Translational oncology
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journal_title:Translational oncology
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journal_title:Translational oncology
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journal_title:Translational oncology
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journal_title:Translational oncology
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journal_title:Translational oncology
pub_type: 杂志文章
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journal_title:Translational oncology
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