BERBERINE COMPLEXES WITH DNA IN THE BERBERINE-INDUCED APOPTOSIS IN HUMAN LEUKEMIC HL-60 CELLS

Berberine, an alkaloid initially isolated from Chinese herbal medicine exhibited the ability to induce morphological changes and internucleo somal DNA fragmentation, characteristic of apoptosis in promyelocytic leukemia HL-60 cells, Cell cycle studies showed that only about 20% of the cells underwent apoptosis at the early time (6 h) of berberine (2 5 mu g/ml) treatment; these appeared to be cells in S phase at the tim e of berberine treatment, At extended time (6-48 h), cells were cell c ycle arrested, the number of cells of each phase, particularly the cel ls of S phase decreased and much more (> 50%) of the cells appeared wi th DNA content less than G(1). Attempts were also made to isolate poss ible berberine-DNA complexes from cell cultures treated with berberine (25 mu g/ml; 2-24 h). Shifts of absorption maxima of berberine in the direction of longer wavelengths were observed in the isolated berberi ne-DNA complexes. Palmatine, an analog of berberine, which was not abl e to induce apoptosis, also complexed with DNA in cells treated with p almatine (25 mu g/ml; 2-24 h), Our results suggest that some important cellular processes other than the intracellular DNA-interacting actio n of berberine may be involved in the berberine-induced apoptosis in H L-60 cells.