Genistein suppresses the inflammation and GSK-3 pathway in an animal model of spontaneous ovarian cancer

Abstract

Background/aim: Numerous studies show that cancer risk is reduced by consumption of soy-based foods containing genistein, but its effects on the glycogen synthase kinase-3 pathway (GSK-3) in ovarian cancer is unknown. Therefore, we tested the properties of genistein on inflammatory biomarkers and GSK-3 signaling pathways in the ovaries of old laying hens with ovarian cancer.

Materials and methods: A total of 300 laying hens were distributed into three groups as follows: group 1, animals fed a standard diet (comprising 22.39 mg of genistein/kg of diet); groups 2 and 3, animals fed a standard diet reconstituted with supplementation of 400 mg or 800 mg of genistein/kg of diet, respectively.

Results: Genistein modulated the inflammatory biomarkers by decreasing serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL- 6), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) compared with control (p < 0.001). Moreover, it upregulated insulin receptor substrate-1 (p-IRS-1) and protein kinase B (p-AKT), but downregulated GSK-3α and β after treatment. It acts in a dose-dependent manner.

Conclusion: Genistein exhibited an anticancer effect by reducing proinflammatory biomarkers levels and inhibiting GSK-3 expression in the ovaries of old laying hens. It is a potential candidate in the chemoprevention and/or treatment of ovarian cancer.

Keywords: GSK-3; Genistein; IL-6; laying hens; ovarian cancer; TNF-α.

Figure 1

Effects of genistein supplementation on IL-6 (A), IL-8 (B), VEGF-C (C), and TNF- α (D) serum protein levels. *p < 0.05, **p < 0.01 statistically different compared with the control group. TNF-α: tumor necrosis factor-alpha; IL-6: interleukin 6; IL-8: interleukin 8; VEGF-C: vascular endothelial growth factor-C.

Figure 2

Effects of genistein supplementation on IL-6 (A), IL-8 (B), VEGF-C (C) and TNF-α (D) protein expression levels in the ovarian samples. The intensity of the bands shown was quantified by densitometric analysis. The bar represents the standard error of the mean. Blots were repeated at least 3 times (n = 3) and a representative blot is shown. β-actin was included to ensure equal protein loading. *p < 0.05, **p < 0.01 statistically different compared with the control group. TNF-α: tumor necrosis factor-alpha; IL-6: interleukin 6; IL-8: interleukin 8; VEGF-C: vascular endothelial growth factor-C.

Figure 3

Effects of genistein supplementation on the expression of the phosphorylated protein p-IRS-1 (A), p-AKT (B), GSK-3α (C), and GSK-3β (D) levels in the ovarian samples. The bar represents the standard error of the mean. Blots were repeated at least 3 times (n = 3) and a representative blot is shown. β-actin was included to ensure equal protein loading. *p < 0.05, **p < 0.01, ***p < 0.001 statistically different compared with the control group. IRS-1: insulin receptor substrate 1; AKT: protein kinase B; GSK-3α and β: glycogen synthase kinase-3 alpha and beta.