Induction of Differentiation and Apoptosis in Three Human Leukemia Cell Lines by a New Compound from Dendrostellera lessertii.

It has previously been shown that Dendrostellera lessertii (Thymelaeaceae) has strong anticancer activity. In this study, the antileukemic activity of another new compound from the same plant extract is reported. Promyelocytic (NB4 and HL-60) and erythroleukemia (K562) cells were cultured in the presence of various concentrations of the new compound (0.5–3.0 μg/ml) for 3 d. The cell numbers were then determined by trypan blue exclusion test. The new compound inhibited growth and proliferation of NB4, HL-60 and K562 with IC₅₀ values of 1.5, 2.0 and 2.5 μg/ml, respectively. We also found that the new compound inhibited cell proliferation in a dose- and time-dependent manner. At low concentrations and after 48 h of treatment, approximately 50%–70% of NB4 and HL-60 cells were differentiated to monocyte/ macrophage lineage and approximately 30%–40% of the treated K562 cells were differentiated in the mega-karyocytic lineage, as evidenced by morphological changes and nitro blue tetrazolium reduction assays. Results of Hoechst 33258 staining also indicated that the new compound induced NB4 and HL-60 cell apoptosis at their respective IC₅₀ values after 72 h of treatment. Based on the present data, the new compound seems a good candidate for further evaluation as an effective chemotherapeutic agent acting through induction of differentiation and apoptosis. [ABSTRACT FROM AUTHOR]