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

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

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 activ...

Full description

Saved in:
Bibliographic Details
Published in:Journal of Oleo Science Vol. 73; no. 7; pp. 991 - 999
Main Authors: Takeguchi, Toru, Kai, Hisahiro, Takeshita, Michika, Miura, Maho, Ogawa, Kenjirou, Nishiyama, Kazuo, Yamasaki, Masao
Format: Journal Article
Language:English
Japanese
Published: Japan Japan Oil Chemists' Society 2024
Japan Science and Technology Agency
Subjects:
cancer cell
Cell death
Cyclohexylamines - pharmacology
Deferoxamine - pharmacology
ferroptosis
Ferroptosis - drug effects
Fractionation
Gel chromatography
Glutathione
Glutathione - metabolism
GPx4
HL-60 Cells
Humans
Inhibitors
Iron Chelating Agents - pharmacology
koji mold
Leukemia
lipid
Lipid Peroxidation - drug effects
Lipids
Membrane Lipids - metabolism
Membranes
Molds
Oxidation-Reduction - drug effects
Peroxidase
Phenylenediamines - pharmacology
Phospholipid Hydroperoxide Glutathione Peroxidase - metabolism
Silica gel
cancer cell
ferroptosis
koji mold
GPx4
lipid
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1345-8957
1347-3352
DOI:10.5650/jos.ess24043