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

Abstract

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.