Kim, Hwan Kim, Nam Doo Lee, Jiyeon Han, Gyoonhee Sim, Taebo 2024-01-20T12:01:41Z 2024-01-20T12:01:41Z 2021-09-05 2013-07-26 0006-291X https://pubs.kist.re.kr/handle/201004/127856 The focal adhesion kinase (FAX) 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 FAX 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 FAX was nearly completely suppressed even with I 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 FAX 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 FAX signaling cascade, which displays strong anti-proliferative activities against a variety of human cancer cells and suppresses adhesion/migration/invasion of tumor cells. (C) 2013 Elsevier Inc. All rights reserved. English ACADEMIC PRESS INC ELSEVIER SCIENCE SMALL-MOLECULE INHIBITOR FAK INHIBITOR Y397 SITE GROWTH MIGRATION PROTEIN BETA Identification of methyl violet 2B as a novel blocker of focal adhesion kinase signaling pathway in cancer cells Article 10.1016/j.bbrc.2013.06.078 1 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.437, no.2, pp.319 - 324 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 437 2 319 324 scie scopus 000323018100022 2-s2.0-84880705839 Biochemistry & Molecular Biology Biophysics Biochemistry & Molecular Biology Biophysics Article SMALL-MOLECULE INHIBITOR FAK INHIBITOR Y397 SITE GROWTH MIGRATION PROTEIN BETA Focal adhesion kinase Methyl violet 28 FAK signaling blocker Structure-based virtual screening FER phosphorylation inhibition Adhesion/migration/invasion suppression