RRC ID 81767
Author Takeguchi T, Kai H, Takeshita M, Miura M, Ogawa K, Nishiyama K, Yamasaki M.
Title Koji Mold-derived Lipids Disrupt the Intracellular Redox State by Decreasing the GPx4 and Intracellular Glutathione Levels, Promoting Membrane Lipid Peroxidation, and Inducing Ferroptosis in HL-60 Cells.
Journal J Oleo Sci
Abstract In this study, we evaluated the cancer cell killing activity of koji mold-derived extracts using several solvents. The koji mold lipid extract (KML) exhibited potent cytotoxicity against a human leukemia cell line. Fractionation of the KML via silica gel chromatography revealed the presence of active components in fraction (Fr.) 6. Cytotoxic effects of Fr. 6 were inhibited by the ferroptosis inhibitors, ferrostatin-1 and SRS11-92, and the iron chelator, deferoxamine. Interestingly, ferroptosis inhibitors failed to prevent the KML-induced cell death. Fr. 6 decreased the expression of glutathione peroxidase 4 (GPx4) and increased the level of peroxidized plasma membrane lipids. Furthermore, Fr. 6 decreased the intracellular glutathione levels. Overall, our results suggest that Fr. 6 included in KML induces ferroptosis in HL-60 cells.
Volume 73(7)
Pages 991-999
Published 2024-1-1
DOI 10.5650/jos.ess24043
PMID 38945927
MeSH Cyclohexylamines / pharmacology Deferoxamine / pharmacology Ferroptosis* / drug effects Glutathione* / metabolism HL-60 Cells Humans Iron Chelating Agents / pharmacology Lipid Peroxidation* / drug effects Lipids Membrane Lipids / metabolism Oxidation-Reduction* / drug effects Phenylenediamines / pharmacology Phospholipid Hydroperoxide Glutathione Peroxidase* / metabolism
IF 1.304
Resource
Human and Animal Cells HL-60