title: Modulating chromatin structure and DNA accessibility by deacetylase inhibition enhances the anti-cancer activity of silver nanoparticles.
abstract: Histone deacetylase (HDAC) inhibitors are considered as novel therapeutic agents inducing cell cycle arrest and apoptotic cell death in various cancer cells. Inhibition of deacetylase activity results in a relaxed chromatin structure thereby rendering the genetic material more vulnerable to DNA targeting agents that could be exploited by combinational cancer therapy. The unique potential of silver nanoparticles (AgNPs) in tumor therapy relies on the generation of reactive radicals which trigger oxidative stress, DNA damage and apoptosis in cancer cells. The revolutionary application of AgNPs as chemotherapeutical drugs seems very promising, nevertheless the exact molecular mechanisms of AgNP action in combination with other anti-cancer agents have yet to be elucidated in details before clinical administrations. As a step towards this we investigated the combinational effect of HDAC inhibition and AgNP administration in HeLa cervical cancer cells. We identified synergistic inhibition of cancer cell growth and migration upon combinational treatments. Here we report that the HDAC inhibitor Trichostatin A enhances the DNA targeting capacity and apoptosis inducing efficacy of AgNPs most probably due to its effect on chromatin condensation. These results point to the potential benefits of combinational application of HDAC inhibitors and AgNPs in novel cancer medication protocols.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Szeged, Középfasor 52, H-6726, Szeged, Hungary.
authors.forename: Nóra
authors.initials: N
authors.lastname: Igaz
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Szeged, Középfasor 52, H-6726, Szeged, Hungary.
authors.forename: Dávid
authors.initials: D
authors.lastname: Kovács
authors.affiliation: Department of Pathology, University of Szeged, Állomás utca 2, H-6720, Szeged, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Rázga
authors.affiliation: Department of Applied and Environmental Chemistry, University of Szeged, Rerrich Béla tér 1, H-6720, Szeged, Hungary; MTA-SZTE Reaction Kinetics and Surface Chemistry Research Group, Rerrich Béla tér 1, H-6720, Szeged, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Kónya
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Szeged, Középfasor 52, H-6726, Szeged, Hungary; Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Temesvári krt. 62, H-6726, Szeged, Hungary.
authors.forename: Imre M
authors.initials: IM
authors.lastname: Boros
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Szeged, Középfasor 52, H-6726, Szeged, Hungary. Electronic address: kiricsim@bio.u-szeged.hu.
authors.forename: Mónika
authors.initials: M
authors.lastname: Kiricsi
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D002843:Chromatin / Q000187:drug effects / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry; D053768:Metal Nanoparticles / Q000737:chemistry*; D012834:Silver / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D012834:Silver; C012589:trichostatin A
keywords: Combinational therapy; Histone acetylation; Silver nanoparticles; Trichostatin A