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  • Title: Ursolic acid inhibits proliferation and induces apoptosis by inactivating Wnt/β-catenin signaling in human osteosarcoma cells.
    Author: Zhang RX, Li Y, Tian DD, Liu Y, Nian W, Zou X, Chen QZ, Zhou LY, Deng ZL, He BC.
    Journal: Int J Oncol; 2016 Nov; 49(5):1973-1982. PubMed ID: 27665868.
    Abstract:
    Although multiple chemotherapeutic agents have been used for osteosarcoma (OS) treatment, their mechanisms need further study. Ursolic acid (UA), a pentacyclic triterpenoid, can reduce cell proliferation and induce apoptosis in various cancer cells, such as OS. However, the exact mechanism underlying this function remains unclear. In this study, we investigated the anti‑proliferative effect of UA in human OS 143B cells and dissected the possible molecular mechanism underlying this effect. We demonstrated that UA can reduce cell proliferation, induce apoptosis and arrest cell cycle in 143B cells, as well as inhibit OS tumor growth in a mouse xenograft model. Using a luciferase reporter assay, we found that the Wnt/β‑catenin signaling is inhibited by UA in 143B cells. Correspondingly, the expression level and nuclear translocation of β‑catenin are both decreased by UA. Exogenous expression of β‑catenin attenuates the anticancer effect of UA in 143B cells, while knockdown of β‑catenin enhances this effect. UA increases the expression level of p53 in a concentration‑dependent manner, and inhibition of p53 reduces the anticancer effect of UA in 143B cells. Moreover, inhibition of p53 partly reverses the UA‑induced downregulation of β‑catenin, as do the targets of Wnt/β‑catenin signaling, such as c‑Myc and cyclin D1. Our findings indicated that UA can inhibit the proliferation of 143B OS cells through inactivation of Wnt/β-catenin signaling, which may be mediated partly by upregulating the expression of p53.
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