Redox Modulation and Induction of Ferroptosis as a New Therapeutic Strategy in Hepatocellular Carcinoma.

Lippmann, Jana; Petri, Kathrin; Fulda, Simone; Liese, Juliane (2020). Redox Modulation and Induction of Ferroptosis as a New Therapeutic Strategy in Hepatocellular Carcinoma. Translational oncology, 13(8), p. 100785. Elsevier 10.1016/j.tranon.2020.100785

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Radiation Oncology

UniBE Contributor:

Lippmann, Jana

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1936-5233

Publisher:

Elsevier

Language:

English

Submitter:

Beatrice Scheidegger

Date Deposited:

08 Jun 2020 12:02

Last Modified:

11 Jun 2020 01:36

Publisher DOI:

10.1016/j.tranon.2020.100785

PubMed ID:

32416440

BORIS DOI:

10.7892/boris.144288

URI:

https://boris.unibe.ch/id/eprint/144288

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