Gentian violet induces wtp53 transactivation in cancer cells

Garufi,Alessia; D'Orazi,Valerio; Arbiser,Jack L.; D'Orazi,Gabriella

doi:10.3892/ijo.2014.2304

Gentian violet induces wtp53 transactivation in cancer cells

Authors:
- Alessia Garufi
- Valerio D'Orazi
- Jack L. Arbiser
- Gabriella D'Orazi
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Affiliations: Department of Experimental Oncology, Regina Elena National Cancer Institute, 00159 Rome, Italy, Department of Surgical Sciences, Sapienza University, 00161 Rome, Italy, Department of Dermatology and Winship Cancer Institute, Emory University School of Medicine, Atlanta Veterans Administration Medical Center, Atlanta, GA, USA
Published online on: February 14, 2014 https://doi.org/10.3892/ijo.2014.2304
Pages: 1084-1090
Copyright: © Garufi et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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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.

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