title: Histone deacetylase inhibitors stimulate the susceptibility of A549 cells to a plasma-activated medium treatment.
abstract: The number of potential applications of non-thermal atmospheric pressure plasma (NTAPP) discharges in medicine, particularly in cancer therapy, has increased in recent years. NTAPP has been shown to affect cells not only by direct irradiation, but also by an indirect treatment with previously prepared plasma-activated medium (PAM). Histone deacetylase (HDAC) inhibitors have the potential to enhance susceptibility to anticancer drugs and radiation. The aim of the present study was to demonstrate the advantage of the combined application of PAM and HDAC inhibitors on A549 cancer cell survival and elucidate the underlying mechanisms. Cell death with DNA breaks in the nucleus was greater using combined regimens of PAM and HDAC inhibitors such as trichostatin A (TSA) and valproic acid (VPA) than a single PAM treatment and was accompanied by the activation of poly (ADP-ribose) polymerase-1 (PARP-1), depletion of ATP, and elevations in intracellular calcium levels. Moreover, the expression of Rad 51, a DNA repair factor in homologous recombination pathways, was significantly suppressed by the treatment with HDAC inhibitors. These results demonstrate that HDAC inhibitors may synergistically induce the sensitivity of cancer cells to PAM components.
authors.affiliation: Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan. Electronic address: adachi@gifu-pu.ac.jp.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Adachi
authors.affiliation: Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors.forename: Ayame
authors.initials: A
authors.lastname: Kano
authors.affiliation: Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors.forename: Saho
authors.initials: S
authors.lastname: Nonomura
authors.affiliation: Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kamiya
authors.affiliation: Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Hara
mesh_terms: D000072283:A549 Cells; D000255:Adenosine Triphosphate / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D016923:Cell Death; D002470:Cell Survival; D003470:Culture Media / Q000737:chemistry; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D015536:Down-Regulation; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000737:chemistry; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy*; D058626:Plasma Gases; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000378:metabolism; D051135:Rad51 Recombinase / Q000378:metabolism; D014635:Valproic Acid / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D003470:Culture Media; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D058626:Plasma Gases; C012589:trichostatin A; D014635:Valproic Acid; D000255:Adenosine Triphosphate; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D006655:Histone Deacetylases; D002118:Calcium
keywords: DNA breaks; Histone deacetylase inhibitor; Non-thermal atmospheric pressure plasma; Plasma-activated medium