Identification of methyl violet 2B as a novel blocker of focal adhesion kinase signaling pathway in cancer cells

Hwan Kim, Nam Doo Kim, Jiyeon Lee, Gyoonhee Han, Taebo Sim

Research output: Contribution to journalArticle

Abstract

The focal adhesion kinase (FAK) signaling cascade in cancer cells was profoundly inhibited by methyl violet 2B identified with the structure-based virtual screening. Methyl violet 2B was shown to be a non-competitive inhibitor of full-length FAK enzyme vs. ATP. It turned out that methyl violet 2B possesses extremely high kinase selectivity in biochemical kinase profiling using a large panel of kinases. Anti-proliferative activity measurement against several different cancer cells and Western blot analysis showed that this substance is capable of suppressing significantly the proliferation of cancer cells and is able to strongly block FAK/AKT/MAPK signaling pathways in a dose dependent manner at low nanomolar concentration. Especially, phosphorylation of Tyr925-FAK that is required for full activation of FAK was nearly completely suppressed even with 1. nM of methyl violet 2B in A375P cancer cells. To the best of our knowledge, it has never been reported that methyl violet possesses anti-cancer effects. Moreover, methyl violet 2B significantly inhibited FER kinase phosphorylation that activates FAK in cell. In addition, methyl violet 2B was found to induce cell apoptosis and to exhibit strong inhibitory effects on the focal adhesion, invasion, and migration of A375P cancer cells at low nanomolar concentrations. Taken together, these results show that methyl violet 2B is a novel, potent and selective blocker of FAK signaling cascade, which displays strong anti-proliferative activities against a variety of human cancer cells and suppresses adhesion/migration/invasion of tumor cells.

Original languageEnglish
Pages (from-to)319-324
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume437
Issue number2
DOIs
Publication statusPublished - 2013 Jul 26

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Gentian Violet
Focal Adhesion Protein-Tyrosine Kinases
Cells
Neoplasms
Phosphotransferases
Phosphorylation
Adhesion
Focal Adhesions
Cell Adhesion
Tumors
Screening
Adenosine Triphosphate
Western Blotting
Chemical activation
Cell Proliferation
Apoptosis

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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title = "Identification of methyl violet 2B as a novel blocker of focal adhesion kinase signaling pathway in cancer cells",
abstract = "The focal adhesion kinase (FAK) signaling cascade in cancer cells was profoundly inhibited by methyl violet 2B identified with the structure-based virtual screening. Methyl violet 2B was shown to be a non-competitive inhibitor of full-length FAK enzyme vs. ATP. It turned out that methyl violet 2B possesses extremely high kinase selectivity in biochemical kinase profiling using a large panel of kinases. Anti-proliferative activity measurement against several different cancer cells and Western blot analysis showed that this substance is capable of suppressing significantly the proliferation of cancer cells and is able to strongly block FAK/AKT/MAPK signaling pathways in a dose dependent manner at low nanomolar concentration. Especially, phosphorylation of Tyr925-FAK that is required for full activation of FAK was nearly completely suppressed even with 1. nM of methyl violet 2B in A375P cancer cells. To the best of our knowledge, it has never been reported that methyl violet possesses anti-cancer effects. Moreover, methyl violet 2B significantly inhibited FER kinase phosphorylation that activates FAK in cell. In addition, methyl violet 2B was found to induce cell apoptosis and to exhibit strong inhibitory effects on the focal adhesion, invasion, and migration of A375P cancer cells at low nanomolar concentrations. Taken together, these results show that methyl violet 2B is a novel, potent and selective blocker of FAK signaling cascade, which displays strong anti-proliferative activities against a variety of human cancer cells and suppresses adhesion/migration/invasion of tumor cells.",
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Identification of methyl violet 2B as a novel blocker of focal adhesion kinase signaling pathway in cancer cells. / Kim, Hwan; Kim, Nam Doo; Lee, Jiyeon; Han, Gyoonhee; Sim, Taebo.

In: Biochemical and Biophysical Research Communications, Vol. 437, No. 2, 26.07.2013, p. 319-324.

Research output: Contribution to journalArticle

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