Berberine induces apoptosis through a mitochondrial/caspase pathway in human promonocytic U937 cells

Berberine, an isoquinoline plant alkaloid, is known to generate a wide variety of biochemical and pharmacological effects. To elucidate the molecular mechanism of berberine-induced antiproliferative activities, the human promonocytic U937 cells were used. Berberine exhibited dose-dependent antiproliferative effects. Morphological evidence of apoptosis, including apoptotic DNA fragmentation, were observed in cells treated with 75 mu g ml(-1) of berberine for 24 h. Flow cytometry analysis revealed that berberine had no effect on cell cycle profile of U937 cells, however, sub-G, fraction (apoptotic cell population) was detected. The percentage of sub-G, fraction of cells treated with 75 mu g ml(-1) of berberine was 25.3 +/- 1.6%. Berberine induces significant changes in mitochondrial membrane potential of U937 cells. The highest tested concentration of berberine decreased the mitochondrial membrane potential to 15.8 +/- 2.4% of control. Additionally, berberine-treated cells had an elevated level of ROS production. Activation of caspase-9 and caspase-3 was also detected, with no caspase-8 activation observed. Taken together, the results clearly demonstrate that berberine induces apoptosis of U937 cells through the mitochondrial/caspase-dependent pathway. (c) 2006 Elsevier Ltd. All rights reserved.