A novel anti-cancer effect of genistein: reversal of epithelial mesenchymal transition in prostate cancer cells¹

Abstract

Aim: The aim of the present study was to investigate whether low dose genistein affects the invasion and epithelial mesenchymal transition (EMT) of prostate cancer (PCa) cells. Methods: Human PCa cell lines, IA8-ARCaP and LNCaP/ HIF-1a, were used in this study. The cell lines were found to process EMT in our previous study. The PCa cells were treated with increasing concentrations, from 0.1 to 75 µmol/L. Proliferation was assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. EMT was proven by cell morphological transition and the expression changes of EMT-related markers, which were confirmed by RT-PCR, Western blotting, and indirect immunofluorescence labeling. Transwell invasion assay was used to analyze the invasive potency. Results: The addition of genistein to the medium reduced the IA8-ARCaP and LNCaP/HIF-1a viable cell number in a dose-dependent manner (with increasing concentrations from 15 to 75 µmol/L). Less than 15 µmol/L genistein was selected as the low dose concentration, which did not affect cell proliferation. The treatment of cells with low-dose genistein induced the reversal of EMT, which was confirmed by cell morphological transition and the expression changes of EMT-related markers. The reversal of EMT in the PCa cells by low-dose genistein was in a dose-dependent manner. Moreover, low-dose genistein effectively inhibited invasion of the PCa cells in vitro. Conclusion: These results showed that treatment with low-dose genistein may be a potential strategy for the suppression of invasive growth through the reversal of EMT in cancer cells, which justifies the potential use of soybean foods as a practical chemopreventive approach for patients with PCa.

Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti-invasive and in vivo anti-metastatic activities

“…In prostate cancer, treating IA8-ARCaP and LNCaP/HIF1a cells with a low dose of genistein effectively inhibited invasion and MET and changes in the expression of EMTrelated markers were also observed [135]. In docetaxelinduced PC3 cells, genistein inhibited invasion and downregulated the expression and activity of MMP-9 [136].…”

Perspectives on the Role of Isoflavones in Prostate Cancer

“…In an in vitro study with two prostate cancer cell lines that possess mesenchymal phenotype, IA8-ARCaP and LNCaP/ HIF-1α, low doses of genistein were found to reverse the mesenchymal phenotype to epithelial phenotype, as evidenced by cell morphology and expression of EMT markers (39). As a further indirect proof, genistein treatment has been shown to attenuate insulin-like growth factor-mediated inhibition of E-cadherin, a marker of epithelial phenotype (40).…”

The role of epithelial plasticity in prostate cancer dissemination and treatment resistance

“…Dietary consumption of another compound, Genistein, an isoflavone found in soy beans, is associated with a lower risk of PC and PC metastasis ([191] and references therein). Interestingly, Genistein treatment results in MET of PC cells, as evidenced by altered biomarker expression and decreased invasion [191].…”

“…Interestingly, Genistein treatment results in MET of PC cells, as evidenced by altered biomarker expression and decreased invasion [191]. Exposure of Genistein also reduces CD44+ cancer stem cells, inhibits the Hedgehog-Gli1 pathway [192], and upregulates miR-574-3p, which decreases proliferation, migration, and invasion of PC cells [193].…”