Emetine exhibits anticancer activity in breast cancer cells as an antagonist of Wnt/β‑catenin signaling

Sun, Qing; Fu, Qiuxia; Li, Shiyue; Li, Junjun; Liu, Shanshan; Wang, Zhongyuan; Su, Zijie; Song, Jiaxing; Lu, Desheng

doi:10.3892/or.2019.7290

Cited by 22 publications

(26 citation statements)

References 42 publications

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“…We note that while the four candidate compounds have been shown to exert antiviral effects against certain virus infections [ 31 , 32 , 33 ], they may also display broad antitumor activity [ 34 , 35 , 36 , 37 ]. Homoharringtonine is the only drug currently approved by the US Food and Drug Administration for the treatment of chronic myeloid leukemia [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Enhancement of the IFN-β-induced host signature informs repurposed drugs for COVID-19

Huang

Chao

Kao

et al. 2020

Heliyon

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a causative agent for the outbreak of coronavirus disease 2019 (COVID-19). This global pandemic is now calling for efforts to develop more effective COVID-19 therapies. Here we use a host-directed approach, which focuses on cellular responses to diverse small-molecule treatments, to identify potentially effective drugs for COVID-19. This framework looks at the ability of compounds to elicit a similar transcriptional response to IFN-β, a type I interferon that fails to be induced at notable levels in response to SARS-CoV-2 infection. By correlating the perturbation profiles of ~3,000 small molecules with a high-quality signature of IFN-β-responsive genes in primary normal human bronchial epithelial cells, our analysis revealed four candidate COVID-19 compounds, namely homoharringtonine, narciclasine, anisomycin, and emetine. We experimentally confirmed that the predicted compounds significantly inhibited SARS-CoV-2 replication in Vero E6 cells at nanomolar, relatively non-toxic concentrations, with half-maximal inhibitory concentrations of 165.7 nM, 16.5 nM, and 31.4 nM for homoharringtonine, narciclasine, and anisomycin, respectively. Together, our results corroborate a host-centric strategy to inform protective antiviral therapies for COVID-19.

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Section: Discussionmentioning

confidence: 99%

Enhancement of the IFN-β-induced host signature informs repurposed drugs for COVID-19

Huang

Chao

Kao

et al. 2020

Heliyon

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“…[14] It is documented that emetine attenuated the Wnt/β-catenin signaling pathway, leading to induction of apoptosis and weakened the migration and invasion of breast cancer. [15] Additionally, emetine suppressed proliferation and the metastatic abilities of lung cancer through the modulation of extracellular signalregulated kinase (ERK) and p38 mitogen-activated protein kinases (MAPKs), as well as the expression of matrix metalloproteinases (MMPs). [16] Those publications imply that emetine may be a promising drug candidate to become repositioned for use in anticancer reagents.…”

Section: Introductionmentioning

confidence: 99%

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

Son

Lee

2021

J Biochem & Molecular Tox

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Osteosarcoma (OS) is a primary bone neoplasm that is highly malignant. As advances in chemotherapy for the treatment of OS have stagnated, 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 the anticancer 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.

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“…Similar to the above-described results, protein synthesis inhibitors exert essential roles in reversing gefitinib resistance. In this class of drugs, three small molecule drugs have been screened, including Emetine, cephaeline and homoharringtonine, among which the antitumor effects of Emetine have been widely reported, the mechanisms are mostly related to inducing apoptosis and blocking the cell cycle 42 . Our in vitro verification results also show that emetine and cephaeline can significantly increase the sensitivity of drug-resistant cells to gefitinib, and the molecular mechanism may be related to the regulation of PI3 and S100A8.…”

Section: Discussionmentioning

confidence: 99%

Identification of Hub Genes and Small Molecule Drugs Associated with Acquired Resistance to Gefitinib in Non-Small Cell Lung Cancer

et al. 2021

J. Cancer

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Targeting EGFR, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), brings lights to the treatment of non-small cell lung cancer (NSCLC). Although T790M mutation responded as one of the main reasons of acquired resistance, still 15% of the resistance patients can't be explained by the known mechanisms. The purpose of this research was to identify some new mechanisms of gefitinib acquired resistance, and to predict small molecules drugs which may reverse drug resistance by integrated bioinformatics analysis. The GSE34228 data package containing the microarray data of acquired gefitinib-resistant cell line (PC9GR) and gefitinib-sensitive cell line (PC9) from the GEO database were downloaded, and gene co-expression networks by weighted gene co-expression network analysis (WGCNA) were constructed to identified key modules and key genes related to gefitinib resistance. Furthermore, the significantly differentially expressed genes (DEGs) between the two cell types were screened out, and a protein-protein interaction (PPI) network to obtain the key genes of DEGs was accordingly constructed. Through the above two methods, 4 hub genes, PI3, S100A8, AXL and PNPLA4 were mined as the most relevant to gefitinib resistance. Among them, PI3, S100A8 were down-regulated in PC9GR cell samples, while AXL, PNPLA4 were up-regulated. The gene set enrichment analysis (GSEA) for single gene showed that the four hub genes were mainly correlated with cell proliferation and cycle. Besides, small molecule drugs with the potential to overcome resistance, such as Emetine and cephaeline, were screened by CMap database. Consistent with this, in vitro experiments results have shown that emetine and cephaeline can increase the sensitivity of drug-resistant cells to gefitinib, and the mechanism may be related to the regulation of PI3 and S100A8. In conclusion, 4 hub genes were found to be related to the occurrence of gefitinib resistance in non-small cell lung cancer, and several small molecule drugs were screened out as potential therapeutic agents to overcome gefitinib resistance, which may lead a new way for the treatment of NSCLC of acquired resistance to gefitinib.

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Emetine exhibits anticancer activity in breast cancer cells as an antagonist of Wnt/β‑catenin signaling

Cited by 22 publications

References 42 publications

Enhancement of the IFN-β-induced host signature informs repurposed drugs for COVID-19

Enhancement of the IFN-β-induced host signature informs repurposed drugs for COVID-19

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

Identification of Hub Genes and Small Molecule Drugs Associated with Acquired Resistance to Gefitinib in Non-Small Cell Lung Cancer

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