Cleavage mechanism and anti-tumor activity of 3,6-epidioxy-1,10-bisaboladiene isolated from edible wild plants

Bioorganic & Medicinal Chemistry
Ken-ichi KimuraHiroyuki Koshino

Abstract

A bisabolane sesquiterpene endoperoxide compound, 3,6-epidioxy-1,10-bisaboladiene (EDBD), was isolated from edible wild plants grown in the northern area of Japan, Cacalia delphiniifolia and Cacalia hastata, using a mutant yeast (cdc2-1 rad9Δ). It showed cytotoxicity at IC(50) = 3.4 μM and induced apoptosis against the human promyelocytic leukemia cell line HL60 through a new stable rearrangement product (1) when in the presence of FeSO(4). This conversion mechanism is different from another sesquiterpene endoperoxide lactone compound, dihydroartemisinin (DHA), which is an anti-malarial drug. The cytotoxicity of EDBD decreased in the presence of the ferrous ion chelating drug deferoxamine mesylate (DFOM), and this suggested that the structural change of the drug caused by Fe(2+) may be responsible for its biological activities. EDBD induced apoptosis via phosphorylation of p38 mitogen-activated protein kinase (MAPK) in HL60 cells, and was detected by Western blot. EDBD resulted in an immediate increase in DCF fluorescence intensity in HL60 cells using DCFH-DA (2',7'-dichlorofluorescin diacetate) assay. The in vitro reaction of EDBD with FeSO(4) also increased DCF fluorescence intensity in a dose dependent manner. These results ...Continue Reading

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Citations

Apr 27, 2017·Journal of Natural Products·Kazuaki KusakabeMasaru Hashimoto
Oct 27, 2017·The Journal of Antibiotics·Yoshihito ShionoKen-Ichi Kimura
Aug 26, 2016·Beilstein Journal of Organic Chemistry·Ivan A YaremenkoAlexander O Terent'ev
May 22, 2019·The Journal of Antibiotics·Ken-Ichi Kimura
Dec 16, 2020·Comprehensive Reviews in Food Science and Food Safety·Zizhan LiPangzhen Zhang

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis