Ursolic acid inhibits proliferation and induces apoptosis by inactivating Wnt/β-catenin signaling in human osteosarcoma cells.
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.
Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing, P.R. China.
Ran-Xi
RX
Zhang
Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing, P.R. China.
Yang
Y
Li
Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing, P.R. China.
Dong-Dong
DD
Tian
Department of Orthopaedics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China.
Yang
Y
Liu
Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing, P.R. China.
Wu
W
Nian
Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing, P.R. China.
Xiang
X
Zou
Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing, P.R. China.
Qian-Zhao
QZ
Chen
Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing, P.R. China.
Lin-Yun
LY
Zhou
Department of Orthopaedics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China.
Zhong-Liang
ZL
Deng
Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing, P.R. China.
Bai-Cheng
BC
He
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008819:Mice, Nude; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*; D000097245:Ursolic Acid
D000972:Antineoplastic Agents, Phytogenic; D014315:Triterpenes; D051176:beta Catenin; D000097245:Ursolic Acid