DOSE-DEPENDENT EFFECTS OF BERBERINE ON CELL-CYCLE PAUSE AND APOPTOSISIN BALB C 3T3 CELLS/

In determining the morphological appearance of Balb/c 3T3 cells from b erberine-treated (100 and 200 mu g/ mi) cultures by light microscopy d emonstrated that the high berberine concentration (200 mu g/ml) treatm ent was associated with the accumulation of numerous apoptotic cells, as identified by condensed nuclei and decrease in cell size. On the ot her hand, accumulation of cells in G(2)/M phase instead of induction o f apoptosis was observed after 48-72 h of 100 mu g/ml berberine treatm ent. Berberine was found mainly in cytoplasm during berberine-induced (100 mu g/ml) cell cycle G(2)/M arrest, while it was highly concentrat ed in nuclei in the induction of apoptosis under high dose of berberin e (200 mu g/ml) treatment. Further addition of berberine (100-200 mu g /ml) had little effect on the induction of apoptosis in the cells that had already been exposed to 100 mu g/ml of berberine for 48 h. Our re sults suggest that there may exist in Balb/c 3T3 cells an important th reshold for regulation of cell cycle pause and induction of apoptosis, that is dose-dependent.