interleukin-8 and daidzein

To develop anti-tumor agents for lung cancer, we aim to characterize a herbal compound, daidzein-rich isoflavones aglycone (DRIA), in inhibiting the proliferation and NF-κB signaling pathway of lung cancer. MTT and colony formation assays were used to analyze the proliferation of lung cancer cells in presence of DRIA treatment, which showed that DRIA dose-dependently inhibited the proliferation and colony formation of lung cancer cells. Enzyme-linked immunosorbent assay revealed that interleukin-6 (IL6) and interleukin-8 (IL-8) levels were reduced by DRIA. p65-NFκB expression and activation, which was enhanced by TNF-α and C/EBPβ treatment, were attenuated by DRIA. Exogenous tumor necrosis factor-α (TNF-α) and CCAAT/enhancer binding protein (C/EBPβ) were used to enhance NF-κB signaling in cells, and the effects of DRIA in attenuating NF-κB signaling were assessed by analyzing p65-NFκB expression in mRNA and protein levels, using quantitative real-time PCR (qRT-PCR), western blot and immunofluorescence staining. immunohistochemical staining revealed that Ki-67 and p65-NF-κB levels in A594 tumor xenografts of A594 tumors were also reduced by DRIA treatment in mice. Our data indicates that DRIA is effective in inhibiting the proliferation and NFκB signaling of lung cancer both in vitro and in vivo.

Topics: Animals; Cell Line, Tumor; Cytokines; Disease Models, Animal; Humans; Interleukin-6; Interleukin-8; Isoflavones; Lung Neoplasms; Mice; NF-kappa B; Signal Transduction; Tumor Necrosis Factor-alpha; Xenograft Model Antitumor Assays

Dysregulated immune responses in the gut to luminal antigens can cause inflammatory bowel diseases (IBD). The roles played by dietary antigens in the pathogenesis or prevention of IBD are poorly understood. Soybean isoflavones are digested in large amounts and have many biological activities. The aim of this study was to determine whether isoflavones in aglycon and bioavailable forms have any effect on gut immunity and protect the host from tissue damage in a mouse model of colitis.. We administered daidzein-rich isoflavone aglycones (DRIA) to mice for 1 week and then treated them with 2% dextran sodium sulfate (DSS) in drinking water for 4 days to induce colitis. The effect of DRIA was evaluated by examining the histopathology of the colon, body weight changes, and functional analysis of mesenteric lymph node cells (MLN).. DRIA inhibited interleukin (IL)-6 and IL-8 production by Toll-like receptor (TLR)2, and TLR4-stimulated monocytes in a dose-dependent manner. The mice administered DRIA had less inflammation and tissue damage in the colon than the control mice. This protective effect of DRIA was associated with a decrease in interferon-gamma, IL-6, and IL-12p40 secretion, and an increase in IL-10 secretion and low cell-activation status of antigen-presenting cells (APC) in MLN.. Ingested DRIA can downregulate the functions of APC and inhibit DSS colitis.

Topics: Animals; Colitis; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Immunity, Innate; Interferon-gamma; Interleukin-10; Interleukin-12; Interleukin-6; Interleukin-8; Isoflavones; Mice; Statistics, Nonparametric; Toll-Like Receptor 2; Toll-Like Receptor 4

High consumption of soy isoflavones in Asian diets has been correlated with a lower incidence of clinically important cases of prostate cancer. The chemopreventive properties of these diets may result from an interaction of several types of isoflavones, including genistein and daidzein. The present study investigated the effects of a soy isoflavone concentrate (ISF) on growth and gene expression profiles of PC-3 human prostate cancer cells. Trypan blue exclusion and [3H]-thymidine incorporation assays showed that ISF decreased cell viability and caused a dose-dependent inhibition of DNA synthesis, respectively, with 50% inhibition (IC50) of DNA synthesis at 52 mg/L (P = 0.05). The glucoside conjugates of genistein and daidzein in ISF were converted to bioactive free aglycones in cell culture in association with the inhibition of DNA synthesis. Flow cytometry and Western immunoblot analyses showed that ISF at 200 mg/L caused an accumulation of cells in the G2/M phase of the cell cycle (P < 0.05) and decreased cyclin A by 20% (P < 0.05), respectively. The effect of ISF on the gene expression profile of PC-3 cells was analyzed using Affymetrix oligonucleotide DNA microarrays that interrogate approximately 17,000 human genes. Of the 75 genes altered by ISF, 28 were upregulated and 47 were downregulated (P < 0.05). Further analysis showed that IL-8, matrix metalloproteinase 13, inhibin beta A, follistatin, and fibronectin mRNA levels were significantly reduced, whereas the expression of p21(CIP1), a major cell cycle inhibitory protein, was increased. The effects of ISF on the expression of IL-8 and p21(CIP1) mRNA and protein were validated at high and low ISF concentrations. Our data show that ISF inhibits the growth of PC-3 cells through modulation of cell cycle progression and the expression of genes involved in cell cycle regulation, metastasis, and angiogenesis.

Topics: DNA; Gene Expression Regulation, Neoplastic; Genistein; Humans; Interleukin-8; Isoflavones; Male; Oligonucleotide Array Sequence Analysis; Phytoestrogens; Prostatic Neoplasms; Soybean Proteins; Tumor Cells, Cultured