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Analogs of genistein and its possible anti-metastatic properties

Marta Świtalska ,  Joanna Wietrzyk ,  Leon Strządała 

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


Background: Genistein is a naturally occurring isoflavonoid, which displays antitumor, proapoptotic, antimetastatic and antiangiogenic properties, described in various experimental in vitro and in vivo models. 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. Integrins comprise a large family of ab heterodimeric cell-surface receptors that present in many species. They are expressed on the wide variety of cells and mediate cell-cell and cell-extracellular matrix interaction.

Objectives: We have examined the effect of genistein, its two new analogs IFG-027 (7-O-alkenyl) and IFG-043 (7-O-arylmethyl) on expression of alfavbeta3 integrins and on adhesion to extracellular matrix protein fibrynogen and fibronectin of human kidney carcinoma A498 cell line.

Methods: Genistein and its analogs were certified synthetic materials obtained from the Pharmaceutical Research Institute, Warsaw, Poland. The human kidney carcinoma cell line A498 was obtained from American Type Culture Collection (ATCC).

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 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 were then labeled by alfavbeta3-specific antibodies conjugated with FITC and expression of integrins was analyzed by flow cytometry (Becton Dickinson, San Jose, CA, U.S.A.).

To determine the influence on cell adhesion, the 96-well flat - bottom plates were coated by fibronectin or fibrynogen. Cells (control and treated by genistein or analogs) were placed in plate for 1 hour in 37ºC and then the plate were washed twice by PBS. The bonded cells were then coloured by crystal violet and we measured absorbance on Multiskan RC photometer at 570 nm wavelength.

Results: We have found that genistein and its new analogs influenced the expression of alfavbeta3 integrins and adhesion to fibrinogen and fibronectin. Genistein decreased the expression of integrins by 20%, whereas IFG-027 analog decreased it by 38% and IFG-043 analog revealed only low influence on the expression of the integrins (decrease by 10%). Only analog IFG-043 inhibited the adhesion of A498 cells to fibronectin (47% of inhibition). IFG-027 and IFG-043 decreased the adhesion to fibrynogen (68% and 92% of inhibition respectively), genistein didn’t have any influence on cell adhesion. Analogs IFG-027 and IFG-043 could be the possible anti-metastatic agents.


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Related papers

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

Submitted: 2010-03-10 08:39
Revised:   2010-03-19 12:36