title: Nanodiamonds coupled with 5,7-dimethoxycoumarin, a plant bioactive metabolite, interfere with the mitotic process in B16F10 cells altering the actin organization.
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.
authors.affiliation: Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Gismondi
authors.affiliation: Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Nanni
authors.affiliation: Department of Chemical Science and Technology, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Reina
authors.affiliation: Department of Chemical Science and Technology, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Orlanducci
authors.affiliation: Department of Chemical Science and Technology, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Terranova
authors.affiliation: Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Canini
mesh_terms: D000199:Actins / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D003374:Coumarins / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D008545:Melanoma / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D058612:Nanodiamonds / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D000199:Actins; D000972:Antineoplastic Agents, Phytogenic; D003374:Coumarins; D058612:Nanodiamonds; C037446:5,7-dimethoxycoumarin
keywords: citropten; cytoskeletal structure; internalization kinetics; melanoma; plant secondary metabolite