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Biochim Biophys Acta Gen Subj. 2017 Nov;1861(11 Pt A):2843-2851. doi: 10.1016/j.bbagen.2017.08.001. Epub 2017 Aug 2.

Antitumour activity of resveratrol on human melanoma cells: A possible mechanism related to its interaction with malignant cell telomerase.

Author information

1
Department of Chemical Sciences, University of Naples Federico II, Via Cintia 21, I-80126 Naples, Italy.
2
Institute of Translational Pharmacology, CNR, Via Fosso del Cavaliere 100, I-00133 Rome, Italy.
3
Laboratory of Molecular Oncology, Istituto Dermopatico dell'Immacolata-IRCCS, Via Monti di Creta, Rome, Italy.
4
School of Medicine, Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier, Rome, Italy.
5
Institute of Biostructures and Bioimages, CNR, Via Mezzocannone 16, I-80134 Naples, Italy. Electronic address: giroviel@unina.it.
6
Department of Chemical Sciences, University of Naples Federico II, Via Cintia 21, I-80126 Naples, Italy; Institute of Biostructures and Bioimages, CNR, Via Mezzocannone 16, I-80134 Naples, Italy. Electronic address: domenica.musumeci@unina.it.
7
Institute of Translational Pharmacology, CNR, Via Fosso del Cavaliere 100, I-00133 Rome, Italy. Electronic address: mariapia.fuggetta@ift.cnr.it.

Abstract

BACKGROUND:

trans-Resveratrol (tRES) is a polyphenolic stilbene found in plant products which has attracted great attention because of its antioxidant, anti-inflammatory and anticancer properties.

METHODS:

The possible correlation between tRES-induced suppression of melanoma cell growth and its influence on telomerase expression has been investigated by biological assays. Moreover, in order to gain new knowledge about possible mechanisms of action of tRES as antineoplastic agent, its interaction with biologically relevant secondary structure-forming DNA sequences, its aggregation properties and copper-binding activity have been studied by CD, UV and fluorescence spectroscopies.

RESULTS:

Biological assays have confirmed that growth inhibitory properties of tRES well correlate with the reduction of telomerase activity and hTERT gene transcript levels in human melanoma cells. Biophysical studies in solution have proved that tRES binds all the studied DNA model systems with low affinity, however showing high ability to discriminate G-quadruplex vs. duplex DNA. In addition, tRES has shown no propensity to form aggregates in the explored concentration range and has been found able to bind Cu2+ ions with a 2:1 stoichiometry.

CONCLUSIONS:

From these biological and biophysical analyses it has emerged that tRES produces cytotoxic effects on human melanoma cells and, at a molecular level, is able to bind Cu2+ and cancer-involved G-quadruplexes, suggesting that multiple mechanisms of action could be involved in its antineoplastic activity.

GENERAL SIGNIFICANCE:

Expanding the knowledge on the putative mechanisms of action of tRES as antitumour agent can help to develop novel, effective tRES-based anticancer drugs.

KEYWORDS:

G-quadruplex DNA; Melanoma cells; Resveratrol; Telomerase activity; Telomeres; hTERT

PMID:
28780124
DOI:
10.1016/j.bbagen.2017.08.001
[Indexed for MEDLINE]

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