3,6-Epidioxy-1,10-bisaboladiene induces ferroptosis-like cell death through lipid peroxidation.

Autor: Usukhbayar N; The United Graduate School of Agricultural Sciences, Iwate University, Morioka, Japan., Takano Y; Graduate School of Agriculture, Iwate University, Morioka, Japan., Uesugi S; The United Graduate School of Agricultural Sciences, Iwate University, Morioka, Japan.; Iwate Biotechnology Research Center, Kitakami, Japan., Muroi M; RIKEN CSRS, Wako, Saitama, Japan., Osada H; RIKEN CSRS, Wako, Saitama, Japan., Kimura KI; The United Graduate School of Agricultural Sciences, Iwate University, Morioka, Japan.; Graduate School of Agriculture, Iwate University, Morioka, Japan.
Jazyk: angličtina
Zdroj: Free radical research [Free Radic Res] 2023 Dec; Vol. 57 (3), pp. 208-222. Date of Electronic Publication: 2023 Jun 30.
DOI: 10.1080/10715762.2023.2229005
Abstrakt: 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 H 2 O 2 -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.
Databáze: MEDLINE
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