Emetine exerts anticancer effects in U2OS human osteosarcoma cells via activation of p38 and inhibitionof ERK, JNK, and β-catenin signaling pathways.

Abstract

Osteosarcoma (OS) is a primary bone neoplasm that is highly malignant. As advances in chemotherapy for the treatment of OS havestagnated, discovery of new reagents is required. Emetine is a phytochemical which can be isolated from a medicinal herb Cephaelis ipecacuanha and is traditionally used for amoebicides. Previous studies have demonstrated that emetine can possibly be repositioned for use in anticancer reagents. However, any anticancer effects and underlying mechanisms of emetine on human OS are not yet well understood. In this study, we analyzed theanticancer effects and involved cellular mechanisms after treatment with emetine to U2OS human OS cells. Emetine significantly reduced both the viability and proliferation, and induced apoptosis via activation of caspase-3 and caspase-7 in U2OS cells. Emetine effectively inhibited the migration and invasion of U2OS cells. Gelatinase activities of matrix metalloproteinase 2 (MMP-2) and MMP-9 were reduced by emetine. MMP-9 was transcriptionally inhibited, while MMP-2 was posttranscriptionally repressed, via the reduced expression of membrane-type I-matrix metalloproteinase (MT1-MMP). p38, which is closely related with induction of apoptosis, was stimulated by emetine. Extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and β-catenin, which are linked with expression of MMPs, were downregulated. Emetine exerted anticancer effects on MG63 human OS cells as well. Taken together, our study demonstrated the anticancer and antimetastatic potential of emetine in treating human OS for the first time. It is expected that emetine may be a promising drug candidate to be repositioned for chemotherapy of OS.