Identification of methyl violet 2B as a novel blocker of focal adhesion kinase signaling pathway in cancer cells
- Identification of methyl violet 2B as a novel blocker of focal adhesion kinase signaling pathway in cancer cells
- 김환; 김남두; 이지연; 한균희; 심태보
- FAK; methyl violet 2B; Focal adhesion kinase; FAK signaling blocker; Structure-based virtual screening; FER phosphorylation inhibition; Adhesion/migration/invasion suppression
- Issue Date
- Biochemical and biophysical research communications
- VOL 437, NO 2, 319-324
- 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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