IC-2 Suppresses Proliferation and Induces Apoptosis of Bladder Cancer Cells via the Wnt/β-Catenin Pathway

Abstract

BackgroundThe Wnt/β-catenin signaling pathway participates in many important tumorigeneses processes, including bladder cancer. The inhibition of abnormal activation of Wnt pathways might provide a new approach to tumor treatment. In the present study, we investigated the role of IC-2, a novel Wnt pathways small molecular inhibitor, in bladder cancer tumorigenesis.Material/MethodsBladder cancer cells were treated with various concentrations of IC-2 (0–5 μM) in vitro. The proliferation ability was measured using colony formation assay and apoptosis was measured using flow cytometry analysis. The protein expression was detected using Western blot analysis. Xenograft in vivo assay was performed to assess tumor growth.ResultsIC-2 suppressed the proliferation and aggravated the apoptosis of bladder cancer cells in dose-dependent and time-dependent manners in vitro. Moreover, high concentrations of IC-2 inhibited the Wnt pathway-related protein expression levels, including β-catenin, Cyclin D1, and TCF4. In vivo, administration of IC-2 in xenograft mice decreased the β-catenin expression and reduced the tumor volume.ConclusionsOur results validate the tumor-inhibition effect of IC-2 on bladder cancer in vivo and in vitro, providing a novel therapeutic strategy for bladder cancer.

Targeting the Wnt/β-catenin signaling pathway in cancer

“…Wnt-C59 (C59), an inhibitor of Wnt, decreased the sphere formation ability of CSCs dosedependently in nasopharyngeal carcinoma (NPC) [151]. IC-2, a novel small-molecule Wnt inhibitor, reduced the population of CD44 + cells (liver CSCs) and the sphereforming ability of hepatocellular carcinoma (HCC) cells, as well as in CRC and bladder cancer cells [152]. In addition, IC-2 increased the sensitivity of 5-FU in the DLD-1 cells, a CRC cell line.…”

Supplementation of Probiotic Butyricicoccus pullicaecorum Mediates Anticancer Effect on Bladder Urothelial Cells by Regulating Butyrate-Responsive Molecular Signatures

“…pullicaecorum -supplemented mice. The expression level of the bladder cancer-associated protein (BLCAP), which is an apoptosis-related tumor suppressor identified from bladder cancer [ 31 , 32 ], was significantly higher (29.2-fold; p < 0.05) in NaB-treated HT1376 cells than that in cells without NaB treatment ( Figure 3 A). Moreover, the immunoreactivity of BLCAP was observed in the layer of transitional epithelium of mouse urinary bladder regardless of whether mice had been treated with B .…”

“…At the same time, we observed increased BLCAP in urothelial bladder cells, not only in the HT1376 cells but also in the 5637 cells ( Supplementary Materials Figure S4 ). BLCAP exhibits a tumor suppressor function in various tumors, including urothelial cancer of the bladder [ 31 ] and can reduce cell growth by stimulating apoptosis [ 32 ]. The increase in BLCAP by B .…”

Ginkgolide C promotes apoptosis and abrogates metastasis of colorectal carcinoma cells by targeting Wnt/β‐catenin signaling pathway

“…Activation of Wnt signaling according to specific cellular environmental stimuli can promote or inhibit apoptosis process 58–60 . A number of reports have shown that Wnt signaling pathway can regulate apoptosis 58,61–64 . Liu et al , identified that nigericin induced apoptosis against CRC via inhibiting Wnt‐related and target proteins 65 .…”