期刊
CANCERS
卷 14, 期 1, 页码 -出版社
MDPI
DOI: 10.3390/cancers14010076
关键词
natural products; sulforaphane; anticancer activity; non-canonical cell death; ferroptosis; necroptosis; apoptosis
类别
资金
- Recherche Cancer et Sang Foundation (Luxembourg)
- Recherches Scientifiques Luxembourg (Luxembourg)
- Een Haerz fir kriibskrank Kanner (Luxembourg)
- Action Lions Vaincre le Cancer (Luxembourg)
- Televie Luxembourg organisations
- National Research Foundation (NRF) [019R1A2C-1009231]
- Brain Korea (BK21) FOUR Program at Seoul National University [370C-20160062]
- Creative-Pioneering Researchers Program at Seoul National University [370C-20160062]
Sulforaphane, a natural anticancer compound, can induce different types of cell death, including apoptosis and ferroptosis, making it a promising agent for anticancer therapy.
Simple Summary Ferroptosis and necroptosis are two non-apoptotic programmed cell death pathways with increasing therapeutic potential. The isothiocyanate sulforaphane (SFN) is a well-known naturally derived anticancer compound with remarkable pro-apoptotic activity. Its ability to promote non-apoptotic cell death mechanisms remains poorly investigated. This work discovered that SFN activates apoptosis and ferroptosis dose-dependently in acute myeloid leukemia cells. At lower concentrations, SFN induces caspase-dependent apoptosis. At higher concentrations, ferroptosis is activated and accompanied by the depletion of intracellular glutathione (GSH) and decreased GSH peroxidase 4 protein expression levels. Necroptosis, instead, is not involved in SFN-induced cell death. Considering that cancer cells resist pro-apoptotic treatments, SFN's ability to induce different types of cell death delineates it as a promising anticancer agent. 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 mu M, SFN induced caspase-dependent apoptosis and at 50 mu M 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.
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