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

Down-Regulation of SOX2 Underlies the Inhibitory Effects of the Triphenylmethane Gentian Violet on Melanoma Cell Self-Renewal and Survival / Pietrobono, Silvia; Morandi, Andrea; Gagliardi, Sinforosa; Gerlini, Gianni; Borgognoni, Lorenzo; Chiarugi, Paola; Arbiser, Jack L; Stecca, Barbara. - In: JOURNAL OF INVESTIGATIVE DERMATOLOGY. - ISSN 0022-202X. - ELETTRONICO. - 136:(2016), pp. 2059-2069-2069. [10.1016/j.jid.2016.06.610]

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

Pietrobono, Silvia;Morandi, Andrea;GAGLIARDI, SINFOROSA;Gerlini, Gianni;Chiarugi, Paola;
2016

Abstract

Human melanomas contain a population of tumor-initiating cells that are able to maintain the growth of the tumor. We previously showed that the embryonic transcription factor SOX2 is essential for self-renewal and tumorigenicity of human melanoma-initiating cells. However, targeting a transcription factor is still challenging. Gentian violet (GV) is a cationic triphenylmethane dye with potent antifungal and antibacterial activity. Recently, a combination therapy of imiquimod and GV has shown an inhibitory effect against melanoma metastases. Whether and how GV affects melanoma cells remains unknown. Here we show that GV represses melanoma stem cell self-renewal through inhibition of SOX2. Mechanistically, GV hinders EGFR activation and inhibits the signal transducer and activator of transcription-3 [(STAT3)/SOX2] axis. Importantly, we show that GV treatment decreases STAT3 phosphorylation at residue tyrosine 705, thus preventing the translocation of STAT3 into the nucleus and its binding to SOX2 promoter. In addition, GV affects melanoma cell growth by promoting mitochondrial apoptosis and G2 cell cycle arrest. This study shows that in melanoma, GV affects both the stem cell and the tumor bulk compartments, suggesting the potential use of GV in treating human melanoma alone or in combination with targeted therapy and/or immunotherapy.
2016
136
2059-2069
2069
Pietrobono, Silvia; Morandi, Andrea; Gagliardi, Sinforosa; Gerlini, Gianni; Borgognoni, Lorenzo; Chiarugi, Paola; Arbiser, Jack L; Stecca, Barbara
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1148019
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