Hot water soluble sesquiterpenes [anhydroperoxy-costunolide and 3-oxoeudesma-1,4(15),11(13)triene-12,6α-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.