RRC ID 78618
Author Usukhbayar N, Takano Y, Uesugi S, Muroi M, Osada H, Kimura KI.
Title 3,6-Epidioxy-1,10-bisaboladiene induces ferroptosis-like cell death through lipid peroxidation.
Journal Free Radic Res
Abstract 3,6-Epidioxy-1,10-bisaboladiene (EDBD) is a bisabolane sesquiterpene endoperoxide that was isolated from an edible wild plant in Japan, Cacalia delphiniifolia. It showed partially apoptotic cell death through caspase activation against HL-60 cells. However, almost all of the cells had necrotic morphology. Thus, we examined the mechanism of action of EDBD on necrotic cell death. EDBD induced ferrous ion-dependent cell death which causes cell membrane damage, and its cell death form was like H2O2-induced necrosis in HL-60 cells. The oxidative stress-induced necrosis inhibitor IM-54 prevented EDBD-induced cell death, but it was not blocked by either caspase inhibitor, z-VAD-fmk, or necroptosis inhibitor, necrostatin-1. Furthermore, EDBD induced lipid peroxidation in a time- and dose-dependent manner and was inhibited with both ferrostatin-1 and α-tocopherol. EDBD also downregulated GPX4, the primary cell defense protein against lipid peroxidation, and decreased GSH levels. Taken together, these results suggest that EDBD induces ferrous ion-dependent ferroptosis-like cell death through lipid peroxidation.
Volume 57(3)
Pages 208-222
Published 2023-12-1
DOI 10.1080/10715762.2023.2229005
PMID 37347979
MeSH Caspases Cell Death Ferroptosis* Humans Hydrogen Peroxide Iron Lipid Peroxidation Necrosis
Human and Animal Cells HL60(RCB0041) HP100-1(RCB0769)