3,6‐Epidioxy‐1,10‐bisaboladiene inhibits G₁‐specific transcription through Swi4/Swi6 and Mbp1/Swi6 via the Hog1 stress pathway in yeast

Abstract

3,6‐Epidioxy‐1,10‐bisaboladiene (EDBD), a bisabolane sesquiterpene endoperoxide compound, was previously isolated from Cacalia delphiniifolia and C. hastata in northern Japan. EDBD has cytotoxic effects and induces apoptosis via phosphorylation of p38 mitogen‐activated protein kinase in human promyelocytic leukemia HL60 cells. However, the mechanism of action of EDBD has not yet been fully elucidated. In this study, we examined the molecular mechanisms of EDBD in the budding yeast Saccharomyces cerevisiae. EDBD arrested the growth of S. cerevisiae cells by suppressing progression from the G1 phase to the S phase and from the G2 phase to the M phase. Moreover, biochemical and genetic analyses revealed that EDBD activated environmental stress–response pathways involving Hog1 and affected Cln3/G1 cyclin activity, thereby inhibiting the expression of SCB‐binding factor and MCB‐binding factor target genes. Our results provided important insights into the functions of EDBD in tumor cells and may facilitate the development of EDBD‐based antitumor therapies. Structured digital abstract •http://www.uniprot.org/uniprot/P25302 http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0915 with http://www.uniprot.org/uniprot/P09959 by http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0007 (http://www.ebi.ac.uk/intact/interaction/EBI-9685387)

Novel Steroidal 5α,8α-Endoperoxide Derivatives with Semicarbazone/Thiosemicarbazone Side-chain as Apoptotic Inducers through an Intrinsic Apoptosis Pathway: Design, Synthesis and Biological Studies

“…(Figure 1) [3][4][5]. Most of natural endoperoxides have been proved with antiviral, anticancer or antifungal activity [6][7][8]. The most representative discovery of endoperoxide from natural products is artemisinin by Youyou Tu (2015 Nobel Award winner) [9].…”

Synthesis of Ergosterol Peroxide Conjugates as Mitochondria Targeting Probes for Enhanced Anticancer Activity

“…Steroidal compounds have drawn attention not only due to unusual and interesting chemical structures but also due to their widespread application as anti-inflammatory, diuretic, anabolic, and anticancer agents [1,2,3,4]. Sterol 5α,8α-endoperoxides are a kind of important active substances in drug discovery, which all have a unique 5α,8α-peroxy moiety (peroxidic bond or peroxide bridge) in the parent structure [5,6,7,8,9,10]. Ergosterol peroxide (5α,8α-epidioxiergosta-6,22-dien-3β-ol, EP, 1 ) is a member of a class of fungal secondary metabolites of sterol endoperoxide derivatives and has been constantly discovered and extracted from different sources of medicinal fungi (Figure 1A) [11,12,13,14].…”