Gentian violet induces wtp53 transactivation in cancer cells

• Type of Material: Article
• Authors: Alessia Garufi, Regina Elena National Cancer Institute; Valerio D'Orazi, Sapienza University; Jack Arbiser, Emory University; Gabriella D'Orazi, Regina Elena National Cancer Institute
• Language: English
• Date: 2014-04
• Publisher: Spandidos Publications
• Publication Version: Final Published Version
• Copyright Statement: © 2014, Spandidos Publications
• License: Creative Commons Attribution-Noncommercial 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.3892/ijo.2014.2304
• Title of Journal or Parent Work: International Journal of Oncology
• ISSN: 1019-6439
• Volume: 44
• Issue: 4
• Start Page: 1084
• End Page: 1090
• Grant/Funding Information: This study was supported by grants from the Italian Association for Cancer Research (AIRC, to G.D.O.) and NIHAR47901, The Rabinowitch-David Foundation, Margolis Foundation and Minsk Foundation (to J.L.A.).
• Keywords: Science & Technology; gene expression; gentian violet; APOPTOSIS; MUTATIONS; HEMANGIOMAS; ONCOLOGY; TRANSFORMATION; MECHANISMS; Life Sciences & Biomedicine; P53 PATHWAY; Oncology; cancer therapy; NADPH oxidase 1; DNA-DAMAGE; p53 transcriptional activity; THERAPY; DNA binding; MAMMALIAN-CELLS; NOX1
• Research Categories: Health Sciences, Oncology; Health Sciences, Medicine and Surgery

Abstract

Recent studies suggest that gentian violet (GV) may have anticancer activity by inhibiting for instance NADPH oxidases (Nox genes) whose overexpression is linked to tumor progression. Nox1 overexpression has been shown to inhibit transcriptional activity of the oncosuppressor p53, impairing tumor cell response to anticancer drugs. The tumor suppressor p53 is a transcription factor that, upon cellular stress, is activated to induce target genes involved in tumor cell growth inhibition and apoptosis. Thus, its activation is important for efficient tumor eradication. In this study, we examined the effect of GV on wild-type (wt) p53 activity in cancer cells. We found that GV was able to overcome the inhibitory effect of the NADPH oxidase Nox1 on p53 transcriptional activity. For the first time we show that GV was able to directly induce p53/DNA binding and transcriptional activity. In vitro, GV markedly induced cancer cell death and apoptotic marker PARP cleavage in wtp53-carrying cells. GV-induced cell death was partly inhibited in cells deprived of p53, suggesting that the anticancer activity of GV may partly depend on p53 activation. GV is US Food and Drug Administration approved for human use and may, therefore, have therapeutic potential in the management of cancer through p53 activation.