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Genistein is a natural compound belonging to isoflavone family of secondary plant metabolites, characterized by pleiotropic biological activity. Here we present the results of a study on new analogs and polysaccharide complexes of genistein as potent antiproliferative and cell death-inducing agents. Most potent were 2 analogs (i.e., IFG-027 and IFG-043) and 2 complexes (i.e., SPG-G and XG-G), which had higher or similar antiproliferative activity in comparison to genistein. However, these 2 analogs decreased the number of cells in G2/M phase in contrast to genistein and SPG-G complex. Genistein analogs, IFG-027 and IFG-043, and also SPG-G complex decreased mitochondrial membrane potential and induced the externalization of phosphatidylserine to the extracellular membrane site, which indicates the induction of apoptosis. Interestingly, genistein and its analogs induced caspase 3-activation supporting apoptotic mechanism of cell death but SPG-G supported caspase 3-independent apoptosis. XG-G complex probably did not induce cell death through the apoptotic pathway, as we did not find the externalization of phosphatidylserine and activation of caspase-3. After the treatment of HL-60 cells with genistein, SPG-G and XG-G formation of acidic vesicular organelle (AVO) was detected. In contrast, in the cells that were treated with genistein analogs IFG-027 and IFG-043, AVO formation was not observed. [ABSTRACT FROM AUTHOR]

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