2-Phenylnaphthyridin-4-one derivative LYF-11 inhibits interleukin-6-mediated epithelial–to–Mesenchymal transition via the inhibition of JAK2/STAT3 signaling pathway in MCF-7 cells

Liang-Chih Liu, Yao Chung Wu, Sheng Chu Kuo, Chi Tang Ho, Tzong Der Way, Shou Tung Chen

Research output: Contribution to journalArticle

Abstract

Background/Aim: Breast tumor interleukin-6 (IL-6) level increases with tumor grade, and elevated serum IL-6 correlates with poor survival in patients with breast cancer. Epithelial–mesenchymal transition (EMT) phenotypes are associated with enhanced metastasis and unfavorable clinical outcome in breast cancer. Therefore, we examined whether IL-6 induced EMT phenotype characterized in breast cancer cells. Materials and Methods: MCF-7 cells treated with different concentrations (10-50 ng/ml) of IL-6 for 24 and 48 h. Western blotting, flow cytometry, and cell migration assay were used to test whether IL-6 promoted tumor-initiating ability in MCF-7 cells. Results: In this study, we found that the induction of EMT by IL-6 resulted in the acquisition of mesenchymal traits and the increase of tumor-initiating ability in MCF-7 cells. Moreover, we found that 2-phenylnaphthy-ridin-4-one derivatives were able to repress IL-6 induced EMT phenotype and tumor-initiating ability. Among these deriveratives, LYF-11 possessed the most potential inhibitory activity. LYF-11 effectively inhibited IL-6induced EMT phenotype and tumor-initiating ability via the inhibition of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Conclusion: Our results suggest a connection between IL-6 receptor activity and EMT phenotype, and tumor-initiating ability. Moreover, LYF-11 is a potential compound for breast cancer therapy by targeting JAK2/STAT3 signaling pathway.

LanguageEnglish (US)
Pages2849-2859
Number of pages11
JournalAnticancer Research
Volume38
Issue number5
DOIs
StatePublished - May 1 2018

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Janus Kinase 2
STAT3 Transcription Factor
Epithelial-Mesenchymal Transition
MCF-7 Cells
Interleukin-6
Breast Neoplasms
Phenotype
Neoplasms
Cell Migration Assays
Interleukin-6 Receptors
Flow Cytometry
Western Blotting
Neoplasm Metastasis
Survival
Serum

Keywords

  • Breast cancer
  • EMT
  • IL-6
  • JAK2/STAT3
  • Tumor-initiating ability

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

2-Phenylnaphthyridin-4-one derivative LYF-11 inhibits interleukin-6-mediated epithelial–to–Mesenchymal transition via the inhibition of JAK2/STAT3 signaling pathway in MCF-7 cells. / Liu, Liang-Chih; Wu, Yao Chung; Kuo, Sheng Chu; Ho, Chi Tang; Way, Tzong Der; Chen, Shou Tung.

In: Anticancer Research, Vol. 38, No. 5, 01.05.2018, p. 2849-2859.

Research output: Contribution to journalArticle

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abstract = "Background/Aim: Breast tumor interleukin-6 (IL-6) level increases with tumor grade, and elevated serum IL-6 correlates with poor survival in patients with breast cancer. Epithelial–mesenchymal transition (EMT) phenotypes are associated with enhanced metastasis and unfavorable clinical outcome in breast cancer. Therefore, we examined whether IL-6 induced EMT phenotype characterized in breast cancer cells. Materials and Methods: MCF-7 cells treated with different concentrations (10-50 ng/ml) of IL-6 for 24 and 48 h. Western blotting, flow cytometry, and cell migration assay were used to test whether IL-6 promoted tumor-initiating ability in MCF-7 cells. Results: In this study, we found that the induction of EMT by IL-6 resulted in the acquisition of mesenchymal traits and the increase of tumor-initiating ability in MCF-7 cells. Moreover, we found that 2-phenylnaphthy-ridin-4-one derivatives were able to repress IL-6 induced EMT phenotype and tumor-initiating ability. Among these deriveratives, LYF-11 possessed the most potential inhibitory activity. LYF-11 effectively inhibited IL-6induced EMT phenotype and tumor-initiating ability via the inhibition of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Conclusion: Our results suggest a connection between IL-6 receptor activity and EMT phenotype, and tumor-initiating ability. Moreover, LYF-11 is a potential compound for breast cancer therapy by targeting JAK2/STAT3 signaling pathway.",
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AU - Wu, Yao Chung

AU - Kuo, Sheng Chu

AU - Ho, Chi Tang

AU - Way, Tzong Der

AU - Chen, Shou Tung

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N2 - Background/Aim: Breast tumor interleukin-6 (IL-6) level increases with tumor grade, and elevated serum IL-6 correlates with poor survival in patients with breast cancer. Epithelial–mesenchymal transition (EMT) phenotypes are associated with enhanced metastasis and unfavorable clinical outcome in breast cancer. Therefore, we examined whether IL-6 induced EMT phenotype characterized in breast cancer cells. Materials and Methods: MCF-7 cells treated with different concentrations (10-50 ng/ml) of IL-6 for 24 and 48 h. Western blotting, flow cytometry, and cell migration assay were used to test whether IL-6 promoted tumor-initiating ability in MCF-7 cells. Results: In this study, we found that the induction of EMT by IL-6 resulted in the acquisition of mesenchymal traits and the increase of tumor-initiating ability in MCF-7 cells. Moreover, we found that 2-phenylnaphthy-ridin-4-one derivatives were able to repress IL-6 induced EMT phenotype and tumor-initiating ability. Among these deriveratives, LYF-11 possessed the most potential inhibitory activity. LYF-11 effectively inhibited IL-6induced EMT phenotype and tumor-initiating ability via the inhibition of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Conclusion: Our results suggest a connection between IL-6 receptor activity and EMT phenotype, and tumor-initiating ability. Moreover, LYF-11 is a potential compound for breast cancer therapy by targeting JAK2/STAT3 signaling pathway.

AB - Background/Aim: Breast tumor interleukin-6 (IL-6) level increases with tumor grade, and elevated serum IL-6 correlates with poor survival in patients with breast cancer. Epithelial–mesenchymal transition (EMT) phenotypes are associated with enhanced metastasis and unfavorable clinical outcome in breast cancer. Therefore, we examined whether IL-6 induced EMT phenotype characterized in breast cancer cells. Materials and Methods: MCF-7 cells treated with different concentrations (10-50 ng/ml) of IL-6 for 24 and 48 h. Western blotting, flow cytometry, and cell migration assay were used to test whether IL-6 promoted tumor-initiating ability in MCF-7 cells. Results: In this study, we found that the induction of EMT by IL-6 resulted in the acquisition of mesenchymal traits and the increase of tumor-initiating ability in MCF-7 cells. Moreover, we found that 2-phenylnaphthy-ridin-4-one derivatives were able to repress IL-6 induced EMT phenotype and tumor-initiating ability. Among these deriveratives, LYF-11 possessed the most potential inhibitory activity. LYF-11 effectively inhibited IL-6induced EMT phenotype and tumor-initiating ability via the inhibition of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Conclusion: Our results suggest a connection between IL-6 receptor activity and EMT phenotype, and tumor-initiating ability. Moreover, LYF-11 is a potential compound for breast cancer therapy by targeting JAK2/STAT3 signaling pathway.

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