The effect of sclareol on growth and cell cycle progression of human leukemic cell lines

Sclareol, a labdane-type diterpene, was tested for cytotoxic effect against a panel of established human leukemic cell lines. The compound showed an I C50 lower than 20 mu g/ml in most cell lines tested, while it was higher fo r resting peripheral blood mononuclear leukocytes (PBML). Furthermore, the compound was tested for cytostatic activity against four of the leukemic ce ll lines used. At a concentration of 20 mu g/ml the compound showed a signi ficant cytostatic effect as soon as 4 h after continuous incubation against two from B and two from T lineage cell lines. The morphology and the kind of death induced from sclareol in three cell lines, was also investigated. The effect of sclareol on the cell cycle progression of two cell lines, usi ng flow cytometry, was examined. The results show that sclareol kills cell lines, through the process of apoptosis. The appearance of the apoptotic si gns is time and dose dependent. From the flow cytometry experiments, a dela y of the cell population on G(0/1) seems to take place. This is the first r eport, that a labdane type diterpene kills tumor cells via a phase specific mechanism which induces apoptosis. (C) 1999 Elsevier Science Ltd. All righ ts reserved.