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Nanodiamonds coupled with 5,7-dimethoxycoumarin, a plant bioactive metabolite, interfere with the mitotic process in B16F10 cells altering the actin organization

Authors Gismondi A, Nanni V, Reina G, Orlanducci S, Terranova ML, Canini A

Received 18 September 2015

Accepted for publication 29 October 2015

Published 3 February 2016 Volume 2016:11 Pages 557—574

DOI https://doi.org/10.2147/IJN.S96614

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Editor who approved publication: Dr Thomas Webster


Angelo Gismondi,1 Valentina Nanni,1 Giacomo Reina,2 Silvia Orlanducci,2 Maria Letizia Terranova,2 Antonella Canini1

1Department of Biology, 2Department of Chemical Science and Technology, University of Rome “Tor Vergata”, Rome, Italy

Abstract: For the first time, we coupled reduced detonation nanodiamonds (NDs) with a plant secondary metabolite, citropten (5,7-dimethoxycoumarin), and demonstrated how this complex was able to reduce B16F10 tumor cell growth more effectively than treatment with the pure molecule. These results encouraged us to find out the specific mechanism underlying this phenomenon. Internalization kinetics and quantification of citropten in cells after treatment with its pure or ND-conjugated form were measured, and it was revealed that the coupling between NDs and citropten was essential for the biological properties of the complex. We showed that the adduct was not able to induce apoptosis, senescence, or differentiation, but it determined cell cycle arrest, morphological changes, and alteration of mRNA levels of the cytoskeletal-related genes. The identification of metaphasic nuclei and irregular disposition of β-actin in the cell cytoplasm supported the hypothesis that citropten conjugated with NDs showed antimitotic properties in B16F10 cells. This work can be considered a pioneering piece of research that could promote and support the biomedical use of plant drug-functionalized NDs in cancer therapy.

Keywords: citropten, cytoskeletal structure, plant secondary metabolite, melanoma, internalization kinetics

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