Journal
FEBS JOURNAL
Volume 281, Issue 20, Pages 4612-4621Publisher
WILEY
DOI: 10.1111/febs.12965
Keywords
3; 6-epidioxy-1; 10-bisaboladiene; G(1) cyclin; Hog1; MCB-binding factor; SCB-binding factor
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3,6-Epidioxy-1,10-bisaboladiene (EDBD), a bisabolane sesquiterpene endoperoxide compound, was previously isolated from Cacaliadelphiniifolia 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 Saccharomycescerevisiae. EDBD arrested the growth of S.cerevisiae cells by suppressing progression from the G(1) phase to the S phase and from the G(2) phase to the M phase. Moreover, biochemical and genetic analyses revealed that EDBD activated environmental stress-response pathways involving Hog1 and affected Cln3/G(1) 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 center dot with by ()
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