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Toxicol In Vitro. 2007 Feb;21(1):25-31. Epub 2006 Aug 25.

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

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Institute of Biochemistry, Nutrition and Health Protection, Faculty of Chemical and Food Technology, Slovak University of Technology, Radlinskeho 9, 81237 Bratislava, Slovakia.


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 microg ml(-1) of berberine for 24h. Flow cytometry analysis revealed that berberine had no effect on cell cycle profile of U937 cells, however, sub-G(0) fraction (apoptotic cell population) was detected. The percentage of sub-G(0) fraction of cells treated with 75 microg 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.

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