关键词: GPx4 cancer cell ferroptosis koji mold lipid

Mesh : Humans HL-60 Cells Phospholipid Hydroperoxide Glutathione Peroxidase / metabolism Ferroptosis / drug effects Lipid Peroxidation / drug effects Glutathione / metabolism Oxidation-Reduction / drug effects Deferoxamine / pharmacology Cyclohexylamines / pharmacology Lipids Phenylenediamines / pharmacology Membrane Lipids / metabolism Iron Chelating Agents / pharmacology

来  源:   DOI:10.5650/jos.ess24043

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.
摘要:
在这项研究中,我们使用几种溶剂评估了曲霉菌提取物的癌细胞杀伤活性。曲霉菌脂质提取物(KML)对人白血病细胞系表现出有效的细胞毒性。通过硅胶色谱法对KML进行分馏,表明馏分中存在活性成分(Fr。)6.Fr的细胞毒性作用。6个被铁凋亡抑制剂抑制,铁抑制素-1和SRS11-92,以及铁螯合剂,去铁胺.有趣的是,铁凋亡抑制剂未能阻止KML诱导的细胞死亡。Fr.6下降了谷胱甘肽过氧化物酶4(GPx4)的表达,增长了质膜脂的过氧化水平。此外,Fr.6降低了细胞内谷胱甘肽程度。总的来说,我们的结果表明FR。KML中包含的图6在HL-60细胞中诱导铁凋亡。
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