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Article

Assessment of gene promoter G‑quadruplex binding and modulation by a naphthalene diimide derivative in tumor cells

  • Authors:
    • Matteo Nadai
    • Graziella Cimino‑Reale
    • Giovanna Sattin
    • Filippo Doria
    • Elena Butovskaya
    • Nadia Zaffaroni
    • Mauro Freccero
    • Manlio Palumbo
    • Sara N. Richter
    • Marco Folini
  • View Affiliations / Copyright

    Affiliations: Department of Molecular Medicine, University of Padova, 35121 Padova, Italy, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy, Department of Organic Chemistry, University of Pavia, 27100 Pavia, Italy, Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy
  • Pages: 369-380
    |
    Published online on: October 23, 2014
       https://doi.org/10.3892/ijo.2014.2723
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Abstract

Naphthalene diimide (NDI) derivatives have shown high affinity for telomeric guanine (G)‑quadruplexes and good antiproliferative activity in different human tumor experimental models. A trisubstituted compound (H‑NDI‑NMe2) has been reported to stabilize the telomeric G‑quadruplex and to cause telomere dysfunction and downregulation of telomerase expression. We further investigated its mechanism of action by analyzing the capability of the molecule to interfere with the expression levels of oncogenes, such as MYC, telome­rase reverse transcriptase (TERT), KIT and BCL2, known to bear G‑quadruplex‑forming sequences within their promoters, in human tumor cell lines of different histological origin. Exposure to H‑NDI‑NMe2 resulted in a cell type‑dependent perturbation of the expression levels of the four selected genes. Biophysical and molecular analyses revealed that H‑NDI‑NMe2 bound with high affinity and effectively stabilized mainly MYC and BCL2, which share long sequences and the possibility of multiple G‑quadruplex folding. The mRNA levels of both genes, but not protein amounts were affected by NDI treatment. Global gene expression analysis showed modulation of genes implicated in telomere function and mechanisms of cancer; however, G‑quadruplex‑mediated regulation of gene expression by H‑NDI‑NMe2 was largely dependent on the cell context. These data indicate that a deeper knowledge on the molecular mechanisms and biological effects of G‑quadruplex structures is still needed to help developing new effective anticancer agents.
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Copy and paste a formatted citation
Spandidos Publications style
Nadai M, Cimino‑Reale G, Sattin G, Doria F, Butovskaya E, Zaffaroni N, Freccero M, Palumbo M, Richter SN, Folini M, Folini M, et al: Assessment of gene promoter G‑quadruplex binding and modulation by a naphthalene diimide derivative in tumor cells. Int J Oncol 46: 369-380, 2015.
APA
Nadai, M., Cimino‑Reale, G., Sattin, G., Doria, F., Butovskaya, E., Zaffaroni, N. ... Folini, M. (2015). Assessment of gene promoter G‑quadruplex binding and modulation by a naphthalene diimide derivative in tumor cells. International Journal of Oncology, 46, 369-380. https://doi.org/10.3892/ijo.2014.2723
MLA
Nadai, M., Cimino‑Reale, G., Sattin, G., Doria, F., Butovskaya, E., Zaffaroni, N., Freccero, M., Palumbo, M., Richter, S. N., Folini, M."Assessment of gene promoter G‑quadruplex binding and modulation by a naphthalene diimide derivative in tumor cells". International Journal of Oncology 46.1 (2015): 369-380.
Chicago
Nadai, M., Cimino‑Reale, G., Sattin, G., Doria, F., Butovskaya, E., Zaffaroni, N., Freccero, M., Palumbo, M., Richter, S. N., Folini, M."Assessment of gene promoter G‑quadruplex binding and modulation by a naphthalene diimide derivative in tumor cells". International Journal of Oncology 46, no. 1 (2015): 369-380. https://doi.org/10.3892/ijo.2014.2723
Copy and paste a formatted citation
x
Spandidos Publications style
Nadai M, Cimino‑Reale G, Sattin G, Doria F, Butovskaya E, Zaffaroni N, Freccero M, Palumbo M, Richter SN, Folini M, Folini M, et al: Assessment of gene promoter G‑quadruplex binding and modulation by a naphthalene diimide derivative in tumor cells. Int J Oncol 46: 369-380, 2015.
APA
Nadai, M., Cimino‑Reale, G., Sattin, G., Doria, F., Butovskaya, E., Zaffaroni, N. ... Folini, M. (2015). Assessment of gene promoter G‑quadruplex binding and modulation by a naphthalene diimide derivative in tumor cells. International Journal of Oncology, 46, 369-380. https://doi.org/10.3892/ijo.2014.2723
MLA
Nadai, M., Cimino‑Reale, G., Sattin, G., Doria, F., Butovskaya, E., Zaffaroni, N., Freccero, M., Palumbo, M., Richter, S. N., Folini, M."Assessment of gene promoter G‑quadruplex binding and modulation by a naphthalene diimide derivative in tumor cells". International Journal of Oncology 46.1 (2015): 369-380.
Chicago
Nadai, M., Cimino‑Reale, G., Sattin, G., Doria, F., Butovskaya, E., Zaffaroni, N., Freccero, M., Palumbo, M., Richter, S. N., Folini, M."Assessment of gene promoter G‑quadruplex binding and modulation by a naphthalene diimide derivative in tumor cells". International Journal of Oncology 46, no. 1 (2015): 369-380. https://doi.org/10.3892/ijo.2014.2723
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