Nigericin Exerts Anticancer Effects on Human Colorectal Cancer Cells by Inhibiting Wnt/β-catenin Signaling Pathway

Liu, Fei; Li, Wei; Hua, Shucheng; Han, Yongtao; Xu, Zhihua; Wan, Daiwei; Wang, Yilin; Chen, Weichang; Kuang, Yuting; Shi, Jian-Quan; Zhi, Qiaoming

doi:10.1158/1535-7163.mct-17-0906

Cited by 26 publications

(21 citation statements)

References 39 publications

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“…Monensin was identified as a selective antineoplastic agent in prostate cancer cell line models 32 and more recently as a selective inhibitor of cancer stemness in induced cancer stem-like tumorspheres 27 . The anti-EMT or anti-CSC properties of nigericin have been studied in different models 33–36 . Thus, this family of monovalent cation ionophores has repeatedly demonstrated cytotoxic effects against cancer cells exhibiting EMT-like or CSC phenotypes although the precise mechanism(s) remain unclear.…”

Section: Discussionmentioning

confidence: 99%

High content screening identifies monensin as an EMT-selective cytotoxic compound

Vanneste¹,

Huang²,

Li³

et al. 2019

Sci Rep

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Epithelial-to-mesenchymal transition (EMT) is implicated in cancer metastasis and drug resistance. Specifically targeting cancer cells in an EMT-like state may have therapeutic value. In this study, we developed a cell imaging-based high-content screening protocol to identify EMT-selective cytotoxic compounds. Among the 2,640 compounds tested, salinomycin and monensin, both monovalent cation ionophores, displayed a potent and selective cytotoxic effect against EMT-like cells. The mechanism of action of monensin was further evaluated. Monensin (10 nM) induced apoptosis, cell cycle arrest, and an increase in reactive oxygen species (ROS) production in TEM 4-18 cells. In addition, monensin rapidly induced swelling of Golgi apparatus and perturbed mitochondrial function. These are previously known effects of monensin, albeit occurring at much higher concentrations in the micromolar range. The cytotoxic effect of monensin was not blocked by inhibitors of ferroptosis. To explore the generality of our findings, we evaluated the toxicity of monensin in 24 human cancer cell lines and classified them as resistant or sensitive based on IC50 cutoff of 100 nM. Gene Set Enrichment Analysis identified EMT as the top enriched gene set in the sensitive group. Importantly, increased monensin sensitivity in EMT-like cells is associated with elevated uptake of 3H-monensin compared to resistant cells.

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Section: Discussionmentioning

confidence: 99%

High content screening identifies monensin as an EMT-selective cytotoxic compound

Vanneste¹,

Huang²,

Li³

et al. 2019

Sci Rep

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“…A newly study by Yakisich et al demonstrated that nigericin might be used in a co-therapy model of lung cancer in combination with other chemotherapeutic agents [27]. Coincidentally, our lab also implied that Wnt/β-catenin signaling might have an essential role in colorectal cancer progression, and nigericin exerted anticancer effects on colorectal cancer cells by directly targeting the β-catenin destruction complex [28]. Furthermore, our recent study has proved the potential toxicity of nigericin on human PC, and revealed the molecular mechanism of nigericin toward PC cells from the perspective of circRNA (31533620).…”

Section: Discussionmentioning

confidence: 56%

Molecular screening for nigericin treatment in pancreatic cancer by high-throughput RNA sequencing

Zhi

Gao

et al. 2020

Preprint

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Background Nigericin, an antibiotic derived from Streptomyces hygroscopicus, has been proved to exhibit promising anti-cancer effects on a variety of cancers. Our previous study investigated the potential anti-cancer properties in pancreatic cancer (PC), and demonstrated that nigericin could inhibited the cell viabilities in concentration- and time-dependent manners via differentially expressed circular RNAs (circRNAs). However, the knowledge of nigericin associated with long non-coding RNA (lncRNA) and mRNA in pancreatic cancer (PC) has not been studied. This study is to elucidate the underlying mechanism from the perspective of lncRNA and mRNA.Methods The continuously varying molecules (lncRNAs and mRNAs) were comprehensively screened by high-throughput RNA sequencing.Results Our data showed that 76 lncRNAs and 172 mRNAs were common differentially expressed in the nigericin anti-cancer process. Subsequently, the bioinformatics analyses, including GO and KEGG analysis, coding and non-coding co-expression network, cis- and trans-regulation predictions and PPI network, were applied to annotate the potential regulatory mechanisms among these coding and non-coding RNAs during the nigericin anti-cancer process.Conclusion These findings provided new insight into the molecular mechanism of nigericin toward cancer cells, and suggested a possible clinical application in PC.

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“…A newly study by Yakisich et al demonstrated that nigericin might be used in a co-therapy model of lung cancer in combination with other chemotherapeutic agents ( 27 ). Coincidentally, our lab also implied that Wnt/β-catenin signaling might have an essential role in colorectal cancer progression, and nigericin exerted anti-cancer effects on colorectal cancer cells by directly targeting the β-catenin destruction complex ( 28 ). Furthermore, our recent study has proved the potential toxicity of nigericin on human PC, and revealed the molecular mechanism of nigericin toward PC cells from the perspective of circRNA ( 23 ).…”

Section: Discussionmentioning

confidence: 95%

Molecular Screening for Nigericin Treatment in Pancreatic Cancer by High-Throughput RNA Sequencing

Gao

Liu

et al. 2020

Front. Oncol.

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Objectives: Nigericin, an antibiotic derived from Streptomyces hygroscopicus, has been proved to exhibit promising anti-cancer effects on a variety of cancers. Our previous study investigated the potential anti-cancer properties in pancreatic cancer (PC), and demonstrated that nigericin could inhibit the cell viabilities in concentration-and time-dependent manners via differentially expressed circular RNAs (circRNAs). However, the knowledge of nigericin associated with long non-coding RNA (lncRNA) and mRNA in pancreatic cancer (PC) has not been studied. This study is to elucidate the underlying mechanism from the perspective of lncRNA and mRNA. Methods: The continuously varying molecules (lncRNAs and mRNAs) were comprehensively screened by high-throughput RNA sequencing. Results: Our data showed that 76 lncRNAs and 172 mRNAs were common differentially expressed in the nigericin anti-cancer process. Subsequently, the bioinformatics analyses, including Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, coding and non-coding co-expression network, cis-and trans-regulation predictions and protein-protein interaction (PPI) network, were applied to annotate the potential regulatory mechanisms among these coding and non-coding RNAs during the nigericin anti-cancer process. Conclusions: These findings provided new insight into the molecular mechanism of nigericin toward cancer cells, and suggested a possible clinical application in PC.

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Nigericin Exerts Anticancer Effects on Human Colorectal Cancer Cells by Inhibiting Wnt/β-catenin Signaling Pathway

Cited by 26 publications

References 39 publications

High content screening identifies monensin as an EMT-selective cytotoxic compound

High content screening identifies monensin as an EMT-selective cytotoxic compound

Molecular screening for nigericin treatment in pancreatic cancer by high-throughput RNA sequencing

Molecular Screening for Nigericin Treatment in Pancreatic Cancer by High-Throughput RNA Sequencing

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