title: Decursinol angelate inhibits PGE2-induced survival of the human leukemia HL-60 cell line via regulation of the EP2 receptor and NFκB pathway.
abstract: Decursinol angelate (DA), an active pyranocoumarin compound from the roots of Angelica gigas, has been reported to possess anti-inflammatory and anti-cancer activities. In a previous study, we demonstrated that prostaglandin E2 (PGE2) plays a survival role in HL-60 cells by protecting them from the induction of apoptosis via oxidative stress. Flow cytometry and Hoechst staining revealed that PGE2 suppresses menadione-induced apoptosis, cell shrinkage, and chromatin condensation, by blocking the generation of reactive oxygen species. Treatment of DA was found to reverse the survival effect of PGE2 as well as restoring the menadione-mediated cleavage of caspase-3, lamin B, and PARP. DA blocked PGE2-induced activation of the EP2 receptor signaling pathway, including the activation of PKA and the phosphorylation of CREB. DA also inhibited PGE2-induced expression of cyclooxygenase-2 and the activation of the Ras/Raf/ Erk pathway, which activates downstream targets for cell survival. Finally, DA greatly reduced the PGE2-induced activation of NF-κB p50 and p65 subunits. These results elucidate a novel mechanism for the regulation of cell survival and apoptosis, and open a gateway for further development and combinatory treatments that can inhibit PGE2 in cancer cells.
authors.affiliation: a School of Life Sciences , BK21 Plus KNU Creative BioResearch Group, Kyungpook National University , Daegu , Korea.|b Department of Biomedical Engineering and Sciences , SMME, National University of Sciences and Technology , Islamabad , Pakistan.
authors.forename: Adeeb
authors.initials: A
authors.lastname: Shehzad
authors.affiliation: a School of Life Sciences , BK21 Plus KNU Creative BioResearch Group, Kyungpook National University , Daegu , Korea.
authors.forename: Salman Ul
authors.initials: SU
authors.lastname: Islam
authors.affiliation: c Department of Herbal Foodceutical Science , Daegu Haany University , Daegu , Korea.
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Ahn
authors.affiliation: d College of Pharmacy , National Basic Research Laboratory of Vascular Homeostasis Regulation, Kyungpook National University , Daegu , Korea.
authors.forename: You Mie
authors.initials: YM
authors.lastname: Lee
authors.affiliation: a School of Life Sciences , BK21 Plus KNU Creative BioResearch Group, Kyungpook National University , Daegu , Korea.
authors.forename: Young Sup
authors.initials: YS
authors.lastname: Lee
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology*; D002087:Butyrates / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D001578:Benzopyrans; D002087:Butyrates; D016328:NF-kappa B; D058307:Receptors, Prostaglandin E, EP2 Subtype; C101278:decursin; D015232:Dinoprostone
keywords: Apoptosis; Decursinol angelate; HL-60 cells; Prostaglandin E2