Saponin Formosanin C-Induced Ferritinophagy and Ferroptosis in Human Hepatocellular Carcinoma Cells
Ferroptosis, a recently discovered form of iron-dependent cell death, requires an increased level of lipid-reactive oxygen species (ROS). Ferritinophagy, a ferritin degradation pathway, depends on a selective autophagic cargo receptor (NCOA4). By screening various types of natural compounds, formosa...
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MDPI AG,
2020-07-01T00:00:00Z.
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LEADER | 00000 am a22000003u 4500 | ||
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001 | doaj_5f1e7c4e17334e6ea535a1bf6d99fcf2 | ||
042 | |a dc | ||
100 | 1 | 0 | |a Pin-Lun Lin |e author |
700 | 1 | 0 | |a Han-Hsuan Tang |e author |
700 | 1 | 0 | |a Shan-Ying Wu |e author |
700 | 1 | 0 | |a Ning-Sing Shaw |e author |
700 | 1 | 0 | |a Chun-Li Su |e author |
245 | 0 | 0 | |a Saponin Formosanin C-Induced Ferritinophagy and Ferroptosis in Human Hepatocellular Carcinoma Cells |
260 | |b MDPI AG, |c 2020-07-01T00:00:00Z. | ||
500 | |a 10.3390/antiox9080682 | ||
500 | |a 2076-3921 | ||
520 | |a Ferroptosis, a recently discovered form of iron-dependent cell death, requires an increased level of lipid-reactive oxygen species (ROS). Ferritinophagy, a ferritin degradation pathway, depends on a selective autophagic cargo receptor (NCOA4). By screening various types of natural compounds, formosanin C (FC) was identified as a novel ferroptosis inducer, characterized by attenuations of FC-induced viability inhibition and lipid ROS formation in the presence of ferroptosis inhibitor. FC also induced autophagic flux, evidenced by preventing autophagic marker LC3-II degradation and increasing yellow LC3 puncta in tandem fluorescent-tagged LC3 (mRFP-GFP) reporter plasmid (ptfLC3) transfected cells when combined with autophagic flux inhibitor. It is noteworthy that FC-induced ferroptosis and autophagic flux were stronger in HepG2 cells expressing higher NCOA4 and lower ferritin heavy chain 1 (FTH1) levels, agreeing with the results of gene expression analysis using CTRP and PRISM, indicating that FTH1 expression level exhibited a significant negative correlation with the sensitivity of the cells to a ferroptosis inducer. Confocal and electron microscopy confirmed the pronounced involvement of ferritinophagy in FC-induced ferroptosis in the cells with elevated NCOA4. Since ferroptosis is a non-apoptotic form of cell death, our data suggest FC has chemotherapeutic potential against apoptosis-resistant HCC with a higher NCOA4 expression via ferritinophagy. | ||
546 | |a EN | ||
690 | |a formosanin C | ||
690 | |a hepatocellular carcinoma | ||
690 | |a ferroptosis | ||
690 | |a autophagy | ||
690 | |a ferritinophagy | ||
690 | |a Therapeutics. Pharmacology | ||
690 | |a RM1-950 | ||
655 | 7 | |a article |2 local | |
786 | 0 | |n Antioxidants, Vol 9, Iss 8, p 682 (2020) | |
787 | 0 | |n https://www.mdpi.com/2076-3921/9/8/682 | |
787 | 0 | |n https://doaj.org/toc/2076-3921 | |
856 | 4 | 1 | |u https://doaj.org/article/5f1e7c4e17334e6ea535a1bf6d99fcf2 |z Connect to this object online. |