Sesquiterpenes (costunolide and zaluzanin D) isolated from laurel (Laurus nobilis L.) induce cell death and morphological change indicative of apoptotic chromatin condensation in leukemia HL-60 cells.
Sesquiterpenes (costunolide and zaluzanin D) were purified from laurel (Laurus nobilis L.) and identified by Mass, and 1H- and 13C-NMR. These 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 11.4, 47.0, and 92.5% after a 3-day-treatment with 5, 10 and 15 micro M costunolide, respectively. The same analysis showed that the hypodiploid nuclei of HL 60 cells were increased to 12.4, 28.9 and 76.7% after a 3-day-treatment with 10, 15 and 20 micro M zaluzanin D, respectively. These findings suggest that growth inhibition by costunolide and zaluzanin D 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.
Hibasami
Hiroshige
H
Faculty of Medicine, Mie University, Tsu-city, Mie 514-0001, Japan.
Yamada
Yayoi
Y
Moteki
Hiroyuki
H
Katsuzaki
Hirotaka
H
Imai
Kunio
K
Yoshioka
Kazumi
K
Komiya
Takashi
T
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002843:Chromatin / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells; D006801:Humans; D027442:Laurus / Q000737:chemistry*; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018629:Spectrometry, Mass, Secondary Ion; D007783:Lactones
D000970:Antineoplastic Agents; D002843:Chromatin; D012717:Sesquiterpenes; C474047:zaluzanin-D; C002602:costunolide; D007783:Lactones