Down-Regulation of SOX2 Underlies the Inhibitory Effects of the Triphenylmethane Gentian Violet on Melanoma Cell Self-Renewal and Survival

作者: Silvia Pietrobono , Andrea Morandi , Sinforosa Gagliardi , Gianni Gerlini , Lorenzo Borgognoni

DOI: 10.1016/J.JID.2016.06.610

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摘要: Human melanomas contain a population of tumor-initiating cells that are able to maintain the growth tumor. We previously showed embryonic transcription factor SOX2 is essential for self-renewal and tumorigenicity human melanoma-initiating cells. However, targeting still challenging. Gentian violet (GV) cationic triphenylmethane dye with potent antifungal antibacterial activity. Recently, combination therapy imiquimod GV has shown an inhibitory effect against melanoma metastases. Whether how affects remains unknown. Here we show represses stem cell through inhibition SOX2. Mechanistically, hinders EGFR activation inhibits signal transducer activator transcription-3 [(STAT3)/SOX2] axis. Importantly, treatment decreases STAT3 phosphorylation at residue tyrosine 705, thus preventing translocation into nucleus its binding promoter. In addition, by promoting mitochondrial apoptosis G2 cycle arrest. This study shows in melanoma, both tumor bulk compartments, suggesting potential use treating alone or targeted and/or immunotherapy.

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