Triptolide, the major component of Chinese herbal medicine Tripterygium wilfordii Hook F, possesses potent anticancer and anti-inflammatory effects. IL-8, a proinflammatory cytokine, is associated with cancer cell proliferation angiogenesis. Here, we found that Triptolide has an inhibitory effect on IL-1β-induced IL-8 expression in human gastric cells, via suppression reactive oxygen species (ROS) production, AP-1, NF-κB activation, which turn affects endothelial angiogenetic activity tumor...

Abstract Metformin, an inexpensive, well-tolerated oral agent that is a commonly used first-line treatment for type 2 diabetes, has become the focus of intense research as potential anticancer agent. In this study, we describe inhibitory effect metformin in interleukin 8 (IL-8) upregulation by lithocholic acid (LCA) HCT116 colorectal cancer (CRC) cells. Pharmacological inhibition studies indicated reactive oxygen species (ROS) were involved LCA-induced IL-8 through activation transcription...

Abstract Immune mechanisms underlying hepatocellular carcinoma (HCC) are not well understood. Here, we show that the Toll-like receptor TLR2 inhibits production of proinflammatory cytokine IL18 and protects mice from DEN-induced liver carcinogenesis. On this protocol, Tlr2−/− exhibited more aggressive HCC development associated with impaired CD8+ T-cell function. Furthermore, Ly6ChighIL18Rα+ myeloid-derived suppressor cells (MDSC) were increased in number livers before tumor onset. MDSC...

The urokinase-type plasminogen activator receptor (uPAR), a glycoprotein localized on the cell surface with glycosylphosphatidylinositol anchor, plays crucial role in invasion, and metastasis of several cancers, including bladder cancer, its expression are significantly negatively correlated patient survival rates. Apigenin, naturally produced phytochemical compound found fruits, vegetables, plant leaves, has been shown to mediate variety cancer-metastasis-related molecules various cancers....

Matrix metalloproteinase-9 (MMP-9) plays a crucial role in cell invasion and cancer metastasis. In this study, we showed that cholic acid (CA), major primary bile acid, can induce MMP-9 expression colon HT29 SW620 cells. CA increased reactive oxygen species (ROS) production also activated phosphorylation of ERK1/2, JNK, p38 MAPK. Specific inhibitors mutagenesis studies ERK1/2 JNK functioned as upstream signals the activation AP-1, MAPK an signal NF-κB. N-acetyl-L-cysteine (NAC, ROS...

Sulforaphane, a natural phytochemical compound found in various cruciferous vegetables, has been discovered to present anti-cancer properties. Matrix metalloproteinase-9 (MMP-9) plays crucial role gastric cancer metastasis. However, the of sulforaphane MMP-9 expression is not yet defined. Nicotine, psychoactive alkaloid tobacco, associated with development cancer. Here, we that suppresses nicotine-mediated induction human cells. We reactive oxygen species (ROS) and MAPKs (p38 MAPK, Erk1/2)...

Panax ginseng was employed in the treatment of "Xiao-Ke" symptom, which nowadays known as diabetes mellitus, traditional Chinese medicine for more than a thousand years. Ginsenoside Re major pharmacologic ingredient found abundantly ginseng. However, anti-diabetic and its underlying mechanism metabolic level are still unclear. Serum urine metabolomic method carried out to investigate pharmacological effects potential on high-fat diet combined streptozotocin-induced type 2 mellitus (T2DM)...

Piperine, a natural alkaloidal pungent product present in pepper plants, possesses the properties of anti-inflammatory and anti-metastasis. Lithocholic acid is monohydroxy-5beta-cholanic with an alpha-hydroxy substituent at position 3; it secondary bile that plays pivotal role fat absorption, has been discovered to mediate colorectal cancer (CRC) cell invasion migration. However, effect piperine on angiogenesis poorly investigated. In current study, we examined LCA-stimulated by measuring...

(-)-Epigallocatechin-3-O-gallate (EGCG), a primary green tea polyphenol, has powerful iron scavengers, belongs to the family of flavonoids with antioxidant properties, and can be used prevent cancer. Urokinase-type plasminogen activator receptors (uPARs) are glycosylphosphatidylinositol (GPI)-anchored cell membrane that have crucial roles in invasion metastasis several cancers including bladder The mechanism action EGCG on uPAR expression not been reported clearly yet. In this study, we...

Abstract Interleukin‐6 (IL‐6), a pleiotropic cytokine, plays key role in endothelial injury and atherosclerosis. In this study, we investigated the effects of nicotine, major psychoactive compound cigarette smoke, on IL‐6 expression EA.hy926 cell invasion. Nicotine stimulated via activator protein 1 (AP‐1) transcription factor. Pharmacological inhibition mutagenesis studies indicated that p38 mitogen‐activated kinase (MAPK) mediated IL‐6‐induced upregulation nicotine cells. Furthermore,...

Micro-RNA-21 (miR-21) is a vital regulator of colorectal cancer (CRC) progression and has emerged as potential therapeutic target in CRC treatment. Our study using real-time PCR assay found that secondary bile acid, lithocholic acid (LCA), stimulated the expression miR21 cell lines. Promoter activity showed LCA strongly promoter HCT116 cells time- dose-dependent manner. Studies chemical inhibitors mutants indicated Erk1/2 signaling, AP-1 transcription factor, STAT3 are major signals involved...

Muscle invasive bladder carcinoma is a highly malignant cancer with high mortality rate, due to its tendency metastasize. The tyrosine kinase recepteur d’origine nantais (RON) promotes metastasis. Lysophosphatidic acid (LPA) phospholipid derivative, which acts as signaling molecule activate three affinity G-protein coupled receptors, LPA1, LPA2, and LPA3. This in turn leads cell proliferation contributes oncogenesis. However, little known about the effects of LPA on (IBC). In this study, we...

Urokinase-type plasminogen activator receptor (uPAR) plays a crucial role in inflammation and tumor metastasis. Docosahexaenoic acid (DHA), representative omega-3 polyunsaturated fatty acid, has been shown to exhibit anti-inflammatory anti-tumor properties. However, the mechanism by which DHA negatively regulates uPAR expression is not yet understood. The aim of this study was investigate effect on 12- O -tetradecanoylphorbol-13-acetate (TPA)-induced potential heme oxygenase-1 (HO-1)...

<p>S. Fig. 2. TLR2 decreases HCC proliferation.</p>

<p>S. Fig. 3. CD45+CD11b+Ly6G-Ly6Chigh cells accumulate in Tlr2-/- mice.</p>

<p>S. Fig. 4. IL-18 expression after DEN injection.</p>

<p>S. Fig. 1. CD8+ T cell function is impaired in Tlr2-/- mice.</p>

<p>S. Fig. 3. CD45+CD11b+Ly6G-Ly6Chigh cells accumulate in Tlr2-/- mice.</p>

<p>S. Fig. 5. IL-18 silencing inhibits MDSC accumulation and restores T cell function.</p>

<p>S. Fig. 6. Caspase-8 expression after DEN/Pam3CSK4 and shcaspase-8 treatment.</p>

<p>S. Fig. 4. IL-18 expression after DEN injection.</p>