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Discovery of Sulforaphane as an Inducer of Ferroptosis in U-937 Leukemia Cells: Expanding Its Anticancer Potential.
- Source :
-
Cancers [Cancers (Basel)] 2021 Dec 24; Vol. 14 (1). Date of Electronic Publication: 2021 Dec 24. - Publication Year :
- 2021
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Abstract
- In recent years, natural compounds have emerged as inducers of non-canonical cell death. The isothiocyanate sulforaphane (SFN) is a well-known natural anticancer compound with remarkable pro-apoptotic activity. Its ability to promote non-apoptotic cell-death mechanisms remains poorly investigated. This work aimed to explore the capacity of SFN to induce non-apoptotic cell death modalities. SFN was tested on different acute myeloid leukemia cell lines. The mechanism of cell death was investigated using a multi-parametric approach including fluorescence microscopy, western blotting, and flow cytometry. SFN triggered different cell-death modalities in a dose-dependent manner. At 25 μM, SFN induced caspase-dependent apoptosis and at 50 μM ferroptosis was induced through depletion of glutathione (GSH), decreased GSH peroxidase 4 protein expression, and lipid peroxidation. In contrast, necroptosis was not involved in SFN-induced cell death, as demonstrated by the non-significant increase in phosphorylation of receptor-interacting protein kinase 3 and phosphorylation of the necroptotic effector mixed lineage kinase domain-like pseudokinase. Taken together, our results suggest that the antileukemic activity of SFN can be mediated via both ferroptotic and apoptotic cell death modalities.
Details
- Language :
- English
- ISSN :
- 2072-6694
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cancers
- Publication Type :
- Academic Journal
- Accession number :
- 35008240
- Full Text :
- https://doi.org/10.3390/cancers14010076