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.
Toru TakeguchiHisahiro KaiMichika TakeshitaMaho MiuraKenjirou OgawaKazuo NishiyamaMasao YamasakiPublished in: Journal of oleo science (2024)
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.
Keyphrases
- cell death
- cell cycle arrest
- induced apoptosis
- fatty acid
- endothelial cells
- reactive oxygen species
- poor prognosis
- acute myeloid leukemia
- endoplasmic reticulum stress
- high glucose
- signaling pathway
- ionic liquid
- diabetic rats
- anti inflammatory
- hydrogen peroxide
- binding protein
- high performance liquid chromatography
- high speed
- tandem mass spectrometry
- high resolution
- induced pluripotent stem cells