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 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.
Jantova
Sona
S
Institute of Biochemistry, Nutrition and Health Protection, Faculty of Chemical and Food Technology, Slovak University of Technology, Radlinskeho 9, 81237 Bratislava, Slovakia.
Cipak
Lubos
L
Letasiova
Silvia
S
D017209:Apoptosis / Q000187:drug effects*; D001599:Berberine / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism / Q000502:physiology; D053181:Caspase 8 / Q000378:metabolism / Q000502:physiology; D053453:Caspase 9 / Q000378:metabolism / Q000502:physiology; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D020298:U937 Cells
D017382:Reactive Oxygen Species; D001599:Berberine; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases