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.