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The new analogs of genistein decrease mitochondrial membrane potential and activate caspase-3

Marta Świtalska 1Grzegorz Grynkiewicz 2Joanna Wietrzyk 1Leon Strządała 1

1. Polish Academy of Sciences, Institute of Immunology and Experimental Therapy (IITD), Rudolfa Weigla 12, Wrocław 53-114, Poland
2. Pharmaceutical Research Institute (IF), Rydygiera 8, Warszawa 01-793, Poland


Background: Genistein is a naturally occurring isoflavonoid, which displays antitumor, antimetastatic and antiangiogenic properties, described in various experimental in vitro and in vivo models [1]. It is a specific inhibitor of protein tyrosine kinase and topoisomerase II. Genistein can arrest cell growth and proliferation, cell cycle at G2/M phase, invasion and angiogenesis [2].

Objectives: We have examined the effect of genistein, its new analogs IFG-027 and IFG-043, and complexes with polymers Xyloglucan x Genistein (XYL) and Schisophylan x Genistein (SCH) on mitochondrial membrane potential and activity of caspase-3 on human promyelocytic leukemia HL-60 cell line.

Methods: Genistein and its analogs and complexes were certified synthetic materials obtained from the Pharmaceutical Research Institute, Warsaw, Poland. The human promyelocytic leukemia cell line HL-60 was obtained from European Type Culture Collection by courtesy of Professor Spik and Dr Mazurier (Laboratory of Biological Chemistry USTL, Lille, France).

The cells were placed in 24-well flat - bottom plates at a density of 1x105 cells per well 24 hours before addition of the tested compounds. The cells were exposed to the test compounds at concentrations of 1, 5 and 10 microg/ml for 72 h. After 72 h of incubation, the cells were collected, washed in phosphate-buffered saline (PBS) and counted in a hemacytometer.

The cells (2x105) were washed twice with PBS. To determined the caspase-3 activity the cells were incubated with PE-conjugated monoclonal rabbit anti-active caspase-3 antibody and to determined the mitochondrial membrane potential the cells were incubated with JC-1. Data analysis was performed by flow cytometry.

Results: All tested compounds decreased mitochondrial membrane potential and the most potent were the analogs, they decreased the potential already in concentration 5 microg/ml (only analog IFG-027 decreased the potential in concentration 1 microg/ml – statistical significant in comparison to control and genistein p≤0.05). Only IFG-027 and IFG-043 (in concentration 10 microg/ml) activated the caspase-3, the more potent was analog IFG-043 - it activate caspase-3 already in concentration 5 microg/ml (statistically significant p≤0.05 as compared to control and genistein).

Conclusions: The analogs of genistein IFG-027 and IFG-043 have very strong proapoptotic activity and may be of potential use in anti-cancer therapy.


[1] Radzikowski Cz et al.: Genistein: a soy isoflavone revealing a pleiotropic mechanism of action-clinical implications in the treatment and prevention of cancer. Postępy Hig Med Dosw, 2004;58:129-140
[2] Ravindranath MH et al.: Anticancer therapeutic potential of soy isoflavone, genistein. Adv Exp Med Biol. 2004;546:121-165


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Related papers

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

Submitted: 2008-03-12 13:46
Revised:   2009-06-07 00:48