| The WNT7B protein has been demonstrated as a secreted signaling molecule in developmental models and cancer cells, but it is unknown that how the dysregulation of Wnt/?-catenin signaling induced by WNT7B acts on tumor progression in hepatocellular carcinoma (HCC). In the present study, high level of WNT7B protein expression was characterized in primary tumors by immunohistochemistry (IHC) and western blot (WB) assay. WNT7B mRNA expression in a spectrum of HCC cell lines was also investigated. Cell viability (CCK-8), reporter (Topflash/Fopflash luciferase activity) and gene expression (Polymerase Chain Reaction (PCR) and WB) based assays revealed abnormity in Wnt/?-catenin transcriptional activity and variable responsiveness to exogenous WNT7B ligand stimulation of gene overexpression in Huh-7. Gene knockdown and reporter studies in HepG2and Huh-7cells confirmed WNT7B mediated cell autonomous Wnt/?-catenin activation, as well as a role in cell invasion and the functions of WNT7B in HCC was possibly accomplished by binding to Frizzled4. Moreover, WNT7B could also suppress the etoposide-induced inhibition of ?-catenin expression. Our findings declare that WNT7B can activate canonical Wnt/?-catenin pathway and modify the HCC cell biological behaviors.The intestinal metabolites of ellagic acid, urolithins were considered as real effective substances to inhibit cancer cell proliferation. The current study investigates the effects of urolithin A on the cell survival of HepG2hepatic carcinoma cell line via Wnt signaling pathway. The antiproliferative effects of UA (0-500?M) on HepG2cells were determined using the CCK assay following12-36h exposure. Effects on ?-catenin and other factors expression were assessed by using real-time PCR and western blot. In present study, urolithin A showed potent antiproliferative activities on HepG2cells. During the cell death induced by UA, the expression of ?-catenin, c-Myc and Cyclin D1were decreased and The TCF/LEF transcriptional activation was noteworthy down-regulated. Urolithin A also activated the protein expression of P53, P38-MAPK and caspase-3, but suppressed the expression of NF-?B p65and other inflammatory mediators. And what's more, the antioxidant assay afforded by UA treatments was associated with decreases in the intracellular ROS levels, and increased SOD and GSH-Px activity in H2O2-treated HepG2cells.Urolithins were the metabolites of ellagic acid by intestinal flora in gastrointestinal tract. In previous research, it was found that urolithins could mainly inhibit prostate cancer and colon cancer cell growth. What's more, we demonstrated the antiproliferative and antioxidant effects of urolithin A, the colonic metabolite of ellagic acid, on hepatocellular carcinoma HepG2cells via Wnt signaling pathaway. However, there is no report about bladder cancer therapy of urolithins. In this paper, three urolithin-type compounds (urolithin A, urolithin B,8-OMe-urolithin A) and ellagic acid were evaluated for antiproliferative activity in vitro against human bladder cancer cell lines T24. The IC50values for T24cell inhibition were43.9,35.2,46.3and33.7?M for urolithin A, urolithin B,8-OMe-urolithin A and ellagic acid, respectively. After the administration of urolithins and ellagic acid, we found these compounds could increase mRNA and protein expression of Phospho-P38MAPK, and decrease mRNA and protein expression of MEKKl and Phospho-c-Jun in T24cells. Caspase-3was also activated and PPAR-y protein expression increased in drug-induced apoptosis. And what's more, the antioxidant assay afforded by three urolithins and EA treatments were associated with decreases in the intracellular ROS and MDA levels, and increased SOD activity in H2O2-treated T24cells.The present study investigated the effects of WNT7B gene on cell proliferation, invasion and gene expression change in hepatocellular carcinoma (HCC), and examined whether WNT7B is involved in activation of canonical Wnt/p-catenin signaling pathway and the nuclear accumulation of ?-catenin (Part ?). In part ? of this study, in vitro antiproliferative and antioxidant effects of urolithin A, the colonic metabolite of ellagic acid, on hepatocellular carcinoma HepG2cells via Wnt signaling pathway, was demonstrated. Crosstalk among Wnt signing deactivation, P38MAPK and NF-?B p65regulation by urolithin A was also discussed. Based on the effect of urolithin A on P38MAPK, the antioxidant and antiproliferative effects of more urolithins, urolithin A, urolithin B and8-OMe-urolithin A were assessed in T24cells, which were urinary tract cancer as well as involved in urolithin metabolism. In conclusion, disrupting the reciprocity between WNT7B and its receptor(s) may be a particularly considerable strategy for therapeutic reversion of dysregulation of Wnt/?-catenin signaling in liver cancer contexts that Wnt activation is mediated by P-catenin upstream effectors rather than mutations in canonical pathway members. The results also suggested that urolithin A could inhibit cell proliferation and reduce the oxidative stress status in liver cancer, and may be considered the "real" effective constituent for HCC prevention and treatment. Moreover, the results suggested that these compounds could suppress cell survial by P38-MAPK and/or c-Jun medicated caspase-3activation and reduce the oxidative stress status in T24bladder cancer. Finally, our study provides the rationale for estimating the anti-cancer effects of natural polyphenols via Wnt signaling and relevant pathway. |
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