Growth inhibitory effect of ethyl acetate-soluble fraction of Cynara cardunculus L. in leukemia cells involves cell cycle arrest, cytochrome c release and activation of caspases.
An extract of artichoke Cynara cardunculus L. (CCE) has been shown to exhibit antioxidant and antigenotoxic properties. In this study, the ability of CCE to inhibit the growth of L1210 and HL-60 leukemia cells was studied. Treatment of leukemia cells with a variety of concentrations of CCE (500-2500 microg/microL) for 24 h resulted in dose-dependent inhibition of leukemia cell growth. The cell growth inhibition was accompanied by G(0)/G(1) cell cycle arrest and by a loss of cells in S phase. Futhermore, apoptosis detected as a sub-G(0) cell population and apoptotic DNA fragmentation was observed. More detailed analyses of apoptosis induced by CCE in HL-60 cells revealed that apoptosis progressed through the caspase-9/-3 pathway, as release of cytochrome c, caspase-9/-3 activations and specific proteolytic cleavage of poly(ADP-ribose) polymerase. Taken together, the results suggest that CCE exerts an antiproliferative activity on leukemia cells and induces apoptosis of these cells through a mitochondrial/caspase dependent pathway.
Nadova
S
S
Department of Genetics, Faculty of Natural Sciences, Comenius University, Mlynska dolina, B-1, 84215 Bratislava, Slovakia.
Miadokova
E
E
Mucaji
P
P
Grancai
D
D
Cipak
L
L
D000085:Acetates / Q000737:chemistry; D000818:Animals; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D031942:Cynara / Q000737:chemistry*; D045304:Cytochromes c / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000378:metabolism / Q000473:pathology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility
D000085:Acetates; D010936:Plant Extracts; C007650:ethyl acetate; D045304:Cytochromes c; D020169:Caspases