Assessment of the Effect of Genistein as a MMP Inhibitor in Proliferation, Apoptosis in Cultured Cells derived from Meningioma, high Grade Glioma, and Low Grade Astrocytoma Brain Tumors

Abstract

Background: Brain tumors of all histological classifications and cell origins, account for great mortality and morbidity worldwide. For many types, especially high grade forms, five-year survival and success rate of surgical treatment is considerably low. This explains why several recent studies have focused on introduction of effective medical therapeutic approaches for treatment of these tumors. Genistein is a member of isoflavonoid family which is proved to have anticancer effects in breast, prostate, and SCCs of various origins. In this article we identify therapeutic effects of Genistein in low grade and high grade gliomas and meningioma.

Materials and Methods: High grade glioma, low grade glioma and meningioma tumors tissue samples were obtained from a total number of 15 patients. Tumor tissues were firstly washed with PBS, cut into small pieces, digested with Collagenase type 1 and cultured in the tissue culture flask containing DMEM and 10% FBS. In passage 3 of culture, cells were treated with different concentrations of Genistein (0,0.01, 1/250,1/500 and 0.001 M) for 72 hours and then IC50for both treated and untreated cellswas evaluated with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Expressions of Fas, p53 and Bcl-2 level were determined using quantitative Real-Time PCR, before and after treatment with Genistein. Data were compared among the case and control groups within studied tumor types and analyzed using Kruskal-Wallis and Mann-Whitney U test.

Results: The results were remarkable for significant reduction of cell viability parameters in Genistein-treated groups of all studied tumor types versus the control groups. This finding comes with documented significant alterations in Fas pathway expression in meningioma and HGG. Also P53 was markedly elevated in HGG, although it was not statistically significant

Conclusion: Results of this study along with previous documentations of anticancer properties of Genistein in other malignancies of various organs, indicates that this compound can effectively act towards tapering of malignant behavior, angiogenesis, and invasion of malignant brain tumors.