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Marta Świtalska 1Anna Komers 1Zbigniew Bortko 1Joanna Wietrzyk 

1. Polish Academy of Sciences, Institute of Immunology and Experimental Therapy (IITD), Rudolfa Weigla 12, Wrocław 53-114, Poland


Genistein, a naturally occurring isoflavonoid, has estrogenic activity and is used as a natural substitute for estrogen replacement therapy in postmenopausal women. Genistein displays antitumor, antimetastatic and antiangiogenic properties, described in various experimental in vitro and in vivo models. We observed that genistein and its new analogs: IGF-027, IFG-043 and polysaccharide complexes: schisophillan x genistein (SG) and xyloglucan x genistein (XG) significantly inhibited the growth of human leukemia cell line HL-60. The ID50 value of genistein was 2.95 mg/ml. The analogs of genistein had stronger antiproliverative activity than genistein (ID50 value of IFG-027 was 0.35 mg/mL, of IGF-043 was 0.41 mg/mL), whereas the complexes had similar antiproliferative properties like genistein (ID50 value of SG - 2.4 m/ml, of XG - 2.15 mg/mL). We studied also the influence of genistein, its analogs and complexes on the cell cycle of HL-60 cell line. The concentration 0.1 mg/mL of this agents was too low to exert some effects on the cell cycle. In concentration 1 mg/mL only IFG-027 and IFG-043 decreased the number of cells in S and G2/M phase and also increased the number of apoptotic cells. Genistein in the highest concentration studied (10 mg/mL) stopped the cells in G2/M phase and increased apoptosis. Additionally decrease in the number of cells in S and G0/G1 phase was observed. The analogs of genistein (in concentration 10 mg/mL) decreased number of cells in S, G0/G1 and G2/M phase and also led the cells to apoptosis. SG complex has weak influence on the cell cycle of HL-60 cells. This agent in concentration 10 mg/ml stopped the cells in G2/M phase and increased the number of cells in G0/G1 phase. XG complex didn't exerts the effects on the cell cycle of HL-60 cells. Then we studied the influence of this compounds (in concentration 1, 5, 10 mg/mL) on the apoptosis and necrosis of HL-60 cells. Genistein, IFG-027, IFG-043 and SG increased number of cells in late apoptosis and necrosis (IFG-027 and IFG-043 showed this effects also in the lowest concentration used (1 mg/mL)). Only IFG-027 and IFG-043 increased the number of cells in the early apoptosis. XG complex didn't exert effects on apoptosis (late and early) and necrosis in concentrations used. The analogs of genistein (IFG-27, IFG-043) have higher antiproliferative and proapoptotic activity but exert different influence on cell cycle than genistein. This two compounds could be considered as lead compounds for further development.

This work was supported by the Foundation for Development of Pharmaceutical Sciences (grant 8/FB/2004, Poland)


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Related papers

Presentation: Poster at V Multidyscyplinarna Konferencja Nauki o Leku, by Marta Świtalska
See On-line Journal of V Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2006-01-30 14:14
Revised:   2009-06-07 00:44