Induction of apoptosis in human leukemia U937 cells by anthocyanins through down-regulation of Bcl-2 and activation of caspases.
Anthocyanins are a class of flavonoids, widely spread throughout the plant kingdom, that exhibit important anti-oxidant and anti-inflammatory actions as well as chemotherapeutic effects. However, little is known concerning the molecular mechanisms by which these activities are exerted. In this study, we investigated the anthocyanins isolated from Vitis coignetiae Pulliat for their potential anti-proliferative and apoptotic effects on human leukemia U937 cells. It was found that these anthocyanins inhibit cell viability and induce apoptotic cell death of U937 cells in a dose-dependent manner, as measured by hemocytometer counts, by alteration in the mitochondrial membrane potential, by increases in sub-G1 populations and by DNA ladder formation. Apoptosis of U937 cells by anthocyanins was associated with modulation of expression of Bcl-2 and IAP family members. Consequently, anthocyanin treatment induced proteolytic activation of caspase-3, -8 and -9, and a concomitant degradation of poly(ADP-ribose) polymerase. However, anthocyanin-induced growth inhibition and apoptosis were significantly attenuated in Bcl-2 overexpressing U937 cells. Furthermore, z-DEVD-fmk, a caspase-3 specific inhibitor, blocked apoptosis and increased the survival of anthocyanin-treated U937 cells. Taken together, these results show that Bcl-2 and caspases are key regulators of apoptosis in response to anthocyanins in human leukemia U937 cells.
Lee
Shin Hwa
SH
Korea Science Academy, Busan 614-822, Korea.
Park
Su Min
SM
Park
Suk Min
SM
Park
Jae Hyeon
JH
Shin
Dong Yeok
DY
Kim
Gi Young
GY
Ryu
Chung Ho
CH
Shin
Sung Chul
SC
Jung
Jin Myung
JM
Kang
Ho Sung
HS
Lee
Won Sup
WS
Choi
Yung Hyun
YH
D000872:Anthocyanins / Q000494:pharmacology*; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism*; D002470:Cell Survival; D004247:DNA / Q000378:metabolism; D015536:Down-Regulation; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008564:Membrane Potentials; D051336:Mitochondrial Membranes / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D020298:U937 Cells; D027843:Vitis / Q000378:metabolism
D000872:Anthocyanins; D019253:Proto-Oncogene Proteins c-bcl-2; D004247:DNA; D020169:Caspases