[Induction of apoptosis by harringtonine and homoharringtonine in HL-60 cells].

Harringtonine (HT) and homoharringtonine (HHT) are two alkaloids isolated from the bark of the evergreen tree Cephalotaxus hainanensis Li in the 1970s. They were found to have activity against murine leukemia, Lewis lung carcinoma and B16 melanoma, and used as anti-leukemia drugs clinically. Apoptosis is an active process of programmed cell suicide and now is believed to be an important target for tumor chemotherapy. In this report, the apoptosis inducing effect of HT and HHT in HL-60 cells were observed. The experiments demonstrated that 2 x 10(-7) mol.L-1 of HT and 10(-7) mol.L-1 of HHT could induce apoptosis in HL-60 cells when the cells were exposed to HT and HHT for 4 h. In agarose gel electrophoresis, DNA extracted from HL-60 cells treated with HT and HHT showed a typical internucleosomal DNA degradation, i.e., DNA ladder and parallel morphological changes as nuclear chromosome segmentation and condensation as well as cytoplasma vacuolation. This effect of HT and HHT was shown to appear in a concentration- and time-dependent manner. The efficacy of HT and HHT in inducing apoptosis of HL-60 cells was found to parallel with their cytotoxic activity in HL-60 cells. These results suggest that the mechanism of antitumor action of HT and HHT is related to their apoptosis inducing activity.