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Biomolecules

Biomolecules

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Iberverin Downregulates GPX4 and SLC7A11 to Induce Ferroptotic Cell Death in Hepatocellular Carcinoma Cells

Published:5 November 2024 DOI: 10.3390/biom14111407 PMID: 39595583
Haoying Yang,?Bolei Dai,?Liangjie Chen,?Yingping Li,?Xiaorui Jin,?Chengchang Gao,?Linfen Han,?Xueli Bian

Abstract

Ferroptosis, a recently elucidated style of regulated cell death, has emerged as a significant area of investigation in cancer biology. Natural active compounds that have anti-cancer effects are promising candidates for cancer prevention. Iberverin, a natural compound derived from Brassica oleracea var. capitata, has been shown to exert anti-tumor activities in some cancers. However, its role in hepatocellular carcinoma (HCC) cells and the molecular mechanisms are still poorly understood. In this study, we proved that iberverin can induce intracellular reactive oxygen species (ROS) generation to inhibit cell proliferation and initiate ferroptotic cell death in HCC cells, which can be eradicated by the ferroptosis inhibitor ferrostatin-1 (Fer-1) or deferoxamine mesylate (DFO) and ROS scavenger (GSH or NAC). Mechanistically, iberverin treatment can simultaneously downregulate SLC7A11 mRNA level and degrade GPX4 through the ubiquitination pathway, leading to lipid peroxidation and ferroptotic cell death in HCC cells. Significantly, a low dose of iberverin can remarkably increase the sensitivity of HCC cells to ferroptosis induced by canonical ferroptosis inducers RSL3 and imidazole ketone erastin (IKE). This study uncovers a critical function of iberverin in preventing HCC through ferroptosis and provides a promising strategy for HCC treatment either via iberverin alone or in combination with canonical ferroptosis inducers in the future.

Substances (14)

Materials
Procduct Name CAS Molecular Formula Supplier Price
DEFEROXAMINE MESYLATE 138-14-7 C26H52N6O11S 292 suppliers $10.00-$2754.00
DEFEROXAMINE MESYLATE 138-14-7 C26H52N6O11S 292 suppliers $10.00-$2754.00
DEFEROXAMINE MESYLATE 138-14-7 C26H52N6O11S 292 suppliers $10.00-$2754.00
DEFEROXAMINE MESYLATE 138-14-7 C26H52N6O11S 292 suppliers $10.00-$2754.00
3-(Methylthio)propyl isothiocyanate 505-79-3 C5H9NS2 170 suppliers $25.00-$1300.00
3-(Methylthio)propyl isothiocyanate 505-79-3 C5H9NS2 170 suppliers $25.00-$1300.00
3-(Methylthio)propyl isothiocyanate 505-79-3 C5H9NS2 170 suppliers $25.00-$1300.00
3-(Methylthio)propyl isothiocyanate 505-79-3 C5H9NS2 170 suppliers $25.00-$1300.00
IKE 1801530-11-9 C35H35ClN6O5 82 suppliers $72.00-$2822.00
IKE 1801530-11-9 C35H35ClN6O5 82 suppliers $72.00-$2822.00

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