Wnt/β-catenin signaling modulates piperine-mediated antitumor effects on human osteosarcoma cells

The plant extract piperine is used as a traditional Chinese medicine due to its anti-inflammatory effects and efficacy against numerous types of cancer. The aim of the present study was to investigate the antitumor mechanism of piperine in human osteosarcoma U2OS and 143B cell lines. The effects of piperine on cell apoptosis and invasion of human osteosarcoma cells were assessed using flow cytometry and Transwell assays. Moreover, western blotting was used to measure the effects of piperine on the protein expression levels of the metastasis markers matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF). In addition, the involvement of the Wnt/β-catenin signaling pathway in modulating the effects of piperine was examined via western blot analysis. The results of MTT and Transwell invasion assays indicated that piperine treatment dose-dependently reduced U2OS and 143B cell viability and invasion. Furthermore, a significant reduction was identified in MMP-2, VEGF, glycogen synthase kinase-3β and β-catenin protein expression levels, as well as the expression levels of their target proteins cyclooxygenase-2, cyclin D1 and c-myc, in U2OS cells after piperine treatment. In addition, similar results were observed in 143B cells. Therefore, the present study demonstrated the efficacy of piperine in osteosarcoma, and identified that the Wnt/β-catenin signaling pathway may modulate the antitumor effects of piperine on human U2OS and 143B cells.