A novel chalcone derivative suppresses melanoma cell growth through targeting Fyn/Stat3 pathway View Full Text


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Article Info

DATE

2020-06-18

AUTHORS

Ling Tang, Jing Long, Keke Li, Xu Zhang, Xiang Chen, Cong Peng

ABSTRACT

BackgroundFyn has been documented to have oncogenic features in multiple tumors, which might be a potential therapeutic target, however, few studies on the function role of Fyn and its specific inhibitors in melanoma.MethodsWe investigated the impacts of Fyn and its inhibitor Lj-1-60 on melanoma through bioinformatics analysis, western blot, cell viability, cell cycle and apoptosis and xenograft tumor model as well as immunohistochemical staining. Pull-down and in vitro kinase assay were used to demonstrate Lj-1-60 targeting Fyn. Transcriptome sequencing and RT-PCR were adopted to confirm the potential mechanisms of Lj-1-60 in melanoma.ResultsOur findings showed that Fyn was overexpressed in melanoma cells and knocked down of Fyn suppressed the proliferation of melanoma cells. To identify the potential inhibitors of Fyn, our in-house library including total of 111,277 chemicals was conducted to vitro screening, among those compounds, 83 inhibitors were further detected to explore the effect on melanoma cells growth and discovered a novel chalcone derivative Lj-1-60 that exhibited low cellular toxicity and high anti-tumor efficacy. Lj-1-60 directly was associated with Fyn and inhibited the Fyn kinase activity with Stat3 as substrate. What’s more, Lj-1-60 suppressed the proliferation of melanoma in vitro and in vivo through inducing cell cycle arrest and apoptosis. Moreover, the activation of Stat3 had also been abrogated both in Lj-1-60 treated melanoma cells or Fyn knocked down cells.ConclusionOur study revealed a novel Fyn inhibitor that could significantly suppress melanoma growth, which is a promising potential inhibitor for melanoma treatment. More... »

PAGES

256

References to SciGraph publications

  • 2018-02-20. TRAF6 regulates EGF-induced cell transformation and cSCC malignant phenotype through CD147/EGFR in ONCOGENESIS
  • 2001-05-03. Constitutive activation of Stat3 by the Src and JAK tyrosine kinases participates in growth regulation of human breast carcinoma cells in ONCOGENE
  • 2014-02-26. Ultraviolet-radiation-induced inflammation promotes angiotropism and metastasis in melanoma in NATURE
  • 2004-04-29. Stat3 activation regulates the expression of matrix metalloproteinase-2 and tumor invasion and metastasis in ONCOGENE
  • 2016-04-11. Understanding the cellular roles of Fyn-related kinase (FRK): implications in cancer biology in CANCER AND METASTASIS REVIEWS
  • 2020-04-14. The phosphorylation of CD147 by Fyn plays a critical role for melanoma cells growth and metastasis in ONCOGENE
  • 2018-11-06. Vitexin compound 1, a novel extraction from a Chinese herb, suppresses melanoma cell growth through DNA damage by increasing ROS levels in JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
  • 2014-03-05. Expression analysis of genes and pathways associated with liver metastases of the uveal melanoma in BMC MEDICAL GENOMICS
  • 2002-09-09. Genomic instability, centrosome amplification, cell cycle checkpoints and Gadd45a in ONCOGENE
  • 2015-05-22. Fyn-phosphorylated PIKE-A binds and inhibits AMPK signaling, blocking its tumor suppressive activity in CELL DEATH & DIFFERENTIATION
  • 2018-06-20. Combating head and neck cancer metastases by targeting Src using multifunctional nanoparticle-based saracatinib in JOURNAL OF HEMATOLOGY & ONCOLOGY
  • 2020-01-30. A novel chalcone derivative has antitumor activity in melanoma by inducing DNA damage through the upregulation of ROS products in CANCER CELL INTERNATIONAL
  • 2016-01-20. Immune-checkpoint blockade — durable cancer control in NATURE REVIEWS CLINICAL ONCOLOGY
  • 2000-05-25. STATs in oncogenesis in ONCOGENE
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    http://scigraph.springernature.com/pub.10.1186/s12935-020-01336-2

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    http://dx.doi.org/10.1186/s12935-020-01336-2

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/32565740


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    79 melanoma growth
    80 melanoma treatment
    81 model
    82 multiple tumors
    83 novel chalcone derivatives
    84 oncogenic features
    85 pathway
    86 potential inhibitors
    87 potential mechanisms
    88 potential therapeutic target
    89 proliferation
    90 proliferation of melanoma
    91 role
    92 sequencing
    93 specific inhibitor
    94 staining
    95 study
    96 substrate
    97 target
    98 therapeutic target
    99 total
    100 toxicity
    101 treatment
    102 tumor model
    103 tumors
    104 viability
    105 vitro
    106 vivo
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