Berberine-antiproliferative activity in vitro and induction of apoptosis/necrosis of the U937 and B16 cells.

Berberine, an isoquinoline plant alkaloid, is widely distributed in plants used in the traditional Chinese medicine. It displays a wide range of biological activities and the mechanism of action. Our previous studies of the anticancer activity of berberine against the cancer cell lines HeLa and L1210 were extended to the human tumour U937 cell line and the murine melanoma B16 cell line growing in vitro. Cytotoxicity was measured by the growth inhibition assay and by the cell morphology monitoring. The in vitro cytotoxic studies were complemented by the cell cycle analysis and determination of apoptotic DNA fragmentation. Berberine acted cytotoxically on both tumour cell lines. The melanoma B16 cells were much more sensitive to berberine treatment than the U937 cells. The value of IC(100) was below 100 microg/ml for the U937 cells and below 1 microg/ml for the B16 cells. As for both cell lines under the long-term influence the values of IC(50) were found to be less than 4 microg/ml. No effect of berberine on the cell cycle profile of the U937 and B16 cells was detected, however, berberine induced apoptosis of the U937 cells. On the other hand, cell lysis/necrosis of the berberine-treated B16 cells was observed as the result of the integrity damage of the cytoplasmic membrane.