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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Main Authors: Pin-Lun Lin (Author), Han-Hsuan Tang (Author), Shan-Ying Wu (Author), Ning-Sing Shaw (Author), Chun-Li Su (Author)
Format: Book
Published: MDPI AG, 2020-07-01T00:00:00Z.
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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.