title: Hot water soluble sesquiterpenes [anhydroperoxy-costunolide and 3-oxoeudesma-1,4(15),11(13)triene-12,6alpha-olide] isolated from laurel (Laurus nobilis L.) induce cell death and morphological change indicative of apoptotic chromatin condensation in leukemia cells.
abstract: Hot water soluble (HWS)-sesquiterpenes [anhydroperoxycostunolide and 3-oxo-eudesma-1,4(15),11(13)triene-12,6alpha-olide] were purified from Laurel (Laurus nobilis L.) and identified by Mass, and 1H- and 13C-NMR. These HWS-sesquiterpenes displayed strong growth inhibitory effect against human promyelotic leukemia HL-60 cells. Apoptotic morphological changes of the nucleus, including chromatin condensation were induced in the HL-60 cells treated with the sesquiterpenes. Flow cytometric analysis showed that the hypodiploid nuclei of HL-60 cells were increased to 10.5, 46.5, and 91.3% after a 3 day-treatment with 2.5, 5 and 10 micromoles anhydroperoxycostunolide, respectively. And the same analysis showed that the hypodiploid nuclei of HL-60 cells were increased to 9.8, 39.2 and 89.6% after a 3 day-treatment with 5, 10 and 20 micromoles 3-oxo-eudesma-1,4(15),11(13)triene-12,6alpha-olide, respectively. These findings suggest that growth inhibition by anhydroperoxycostunolide and 3-oxo-eudesma-1,4(15),11(13)triene-12,6alpha-olide of HL-60 cells results from the induction of chromatin condensation in the HL-60 cells. On the other hand, fragmentations by these compounds of DNA to oligonucleosomal-sized fragments were not observed in the HL-60 cells.
authors.affiliation: Faculty of Bioresources, Mie University, Tsu-city, Mie 514-0001, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Komiya
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Yamada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Moteki
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Katsuzaki
authors.forename: Kunio
authors.initials: K
authors.lastname: Imai
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Hibasami
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002843:Chromatin / Q000187:drug effects* / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D027442:Laurus / Q000737:chemistry*; D007938:Leukemia / Q000188:drug therapy / Q000473:pathology; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045787:Sesquiterpenes, Eudesmane / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D012995:Solubility
chemical_list: C488485:3-oxo-eudesma-1,4(15),11(13)triene-12,6alpha-olide; D002843:Chromatin; D010936:Plant Extracts; D012717:Sesquiterpenes; D045787:Sesquiterpenes, Eudesmane; C488484:anhydroperoxycostunolide