Cytotoxic activity and antiproliferative effects of a new semi-synthetic derivative of ent-3 beta-hydroxy-13-epi-manoyl oxide on human leukemic cell lines
K. Dimas et al., Cytotoxic activity and antiproliferative effects of a new semi-synthetic derivative of ent-3 beta-hydroxy-13-epi-manoyl oxide on human leukemic cell lines, ANTICANC R, 19(5B), 1999, pp. 4065-4072
Ent-3 beta-hydroxy-13-epi-manoyl oxide (1), was converted to its thiomidazo
lide derivative (2) which was tested for its cytotoxic activity against a p
anel of established human leukemic cell lines. Compound 2, exhibited cytoto
xic activity against 13 of the cell lines tested. Additionally: compound 2
was examined for its effect on the uptake of [H-3]-thymidine as a marker of
DNA synthesis and on cell proliferation. The morphology of the cells and t
he kind of death induced, was investigated. Flow cytometry experiments on a
leukemic cell line was also performed. The results show that the semi- syn
thetic compound, showed a significant antiproliferative effect and kills ce
lls through the process of apoptosis. The appearence of the apoptotic signs
was time and close dependent. From the flow cytometry experiments, a synch
ronisation through a delay of the cells in G(0/1), phase seems to take plac
e.