Abstract
Nitric oxide (NO) exerts its function in several cell and organ compartments. Recently, several lines of evidence have been accrued showing that NO can play a critical role in oncogenesis. Here we summarize some of these findings and highlight the role of NO as a possible target for antineoplastic drugs. Specifically, NO appears to affect some aspects of neuronal tumour progression, particularly the chemoresistance phenotype, through inhibition of MYC activity and expression of a large set of ATP binding cassette transporters. Here we provide lines of evidence supporting the view that MYCN can alter expression of several members of the ABC transporter family thus influencing the chemoresistance phenotype of neuroblastoma cells. Furthermore, we show that increased intracellular NO concentration either through addition of NO donors to culture medium or through forced expression of nNOS in neuroblastoma cells leads to decreased expression of MYCN and ABC drug transporter genes. Overall, data reviewed here and novel results presented, unveil a NO-MYCN-ABC transporters axis with important implication on development and control of the chemoresistance phenotype in neuronal tumours.
Keywords: MYCN, nitric oxide, ABC transporter genes, neuronal tumours, neuroblastoma
Current Pharmaceutical Design
Title: Nitric Oxide Control of MYCN Expression and Multi Drug Resistance Genes in Tumours of Neural Origin
Volume: 16 Issue: 4
Author(s): Antonio Porro, Christophe Chrochemore, Francesco Cambuli, Nunzio Iraci, Antonio Contestabile and Giovanni Perini
Affiliation:
Keywords: MYCN, nitric oxide, ABC transporter genes, neuronal tumours, neuroblastoma
Abstract: Nitric oxide (NO) exerts its function in several cell and organ compartments. Recently, several lines of evidence have been accrued showing that NO can play a critical role in oncogenesis. Here we summarize some of these findings and highlight the role of NO as a possible target for antineoplastic drugs. Specifically, NO appears to affect some aspects of neuronal tumour progression, particularly the chemoresistance phenotype, through inhibition of MYC activity and expression of a large set of ATP binding cassette transporters. Here we provide lines of evidence supporting the view that MYCN can alter expression of several members of the ABC transporter family thus influencing the chemoresistance phenotype of neuroblastoma cells. Furthermore, we show that increased intracellular NO concentration either through addition of NO donors to culture medium or through forced expression of nNOS in neuroblastoma cells leads to decreased expression of MYCN and ABC drug transporter genes. Overall, data reviewed here and novel results presented, unveil a NO-MYCN-ABC transporters axis with important implication on development and control of the chemoresistance phenotype in neuronal tumours.
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Porro Antonio, Chrochemore Christophe, Cambuli Francesco, Iraci Nunzio, Contestabile Antonio and Perini Giovanni, Nitric Oxide Control of MYCN Expression and Multi Drug Resistance Genes in Tumours of Neural Origin, Current Pharmaceutical Design 2010; 16 (4) . https://dx.doi.org/10.2174/138161210790232112
DOI https://dx.doi.org/10.2174/138161210790232112 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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