Increased histone deacetylase activity involved in the suppressed invasion of cancer cells survived from ALA-mediated photodynamic treatment
Journal
International Journal of Molecular Sciences
Journal Volume
16
Journal Issue
10
Pages
23994-24010
Date Issued
2015
Author(s)
Abstract
Previously, we have found that cancer cells survived from 5-Aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) have abnormal mitochondrial function and suppressed cellular invasiveness. Here we report that both the mRNA expression level and enzymatic activity of histone deacetylase (HDAC) were elevated in the PDT-derived variants with dysfunctional mitochondria. The activated HDAC deacetylated histone H3 and further resulted in the reduced migration and invasion, which correlated with the reduced expression of the invasion-related genes, matrix metalloproteinase 9 (MMP9), paternally expressed gene 1 (PEG1), and miR-355, the intronic miRNA. Using chromatin immunoprecipitation, we further demonstrate the reduced amount of acetylated histone H3 on the promoter regions of MMP9 and PEG1, supporting the down-regulation of these two genes in PDT-derived variants. These results indicate that HDAC activation induced by mitochondrial dysfunction could modulate the cellular invasiveness and its related gene expression. This argument was further verified in the 51-10 cybrid cells with the 4977 bp mtDNA deletion and A375 ρ0 cells with depleted mitochondria. These results indicate that mitochondrial dysfunction might suppress tumor invasion through modulating histone acetylation. ? 2015 by the authors; licensee MDPI, Basel, Switzerland.
SDGs
Other Subjects
acetyl coenzyme A; aminolevulinic acid; cytochrome c oxidase; E1A associated p300 protein; epidermal growth factor receptor; gelatinase B; histone acetyltransferase GCN5; histone acetyltransferase PCAF; histone deacetylase; histone deacetylase 1; histone deacetylase 2; histone deacetylase 3; histone H3; microRNA; microRNA 355; unclassified drug; aminolevulinic acid; azacitidine; gelatinase B; histone; histone deacetylase; histone deacetylase inhibitor; hydroxamic acid; mesoderm specific transcript protein; microRNA; MIRN355 microRNA, human; MMP9 protein, human; protein; trichostatin A; Article; cancer cell; cancer inhibition; cell invasion assay; cell migration assay; cell survival; chemiluminescence immunoassay; chromatin immunoprecipitation; controlled study; down regulation; enzyme activity; gene; histone acetylation; human; human cell; mitochondrial DNA depletion; mRNA expression assay; paternally expressed gene 1; photodynamic therapy; photodynamics; real time polymerase chain reaction; reverse transcription polymerase chain reaction; Western blotting; acetylation; biosynthesis; cell motion; genetics; metabolism; mitochondrion; pathology; photochemotherapy; physiology; procedures; promoter region; tumor cell line; tumor invasion; Acetylation; Aminolevulinic Acid; Azacitidine; Cell Line, Tumor; Cell Movement; Chromatin Immunoprecipitation; Histone Deacetylase Inhibitors; Histone Deacetylases; Histones; Humans; Hydroxamic Acids; Matrix Metalloproteinase 9; MicroRNAs; Mitochondria; Neoplasm Invasiveness; Photochemotherapy; Promoter Regions, Genetic; Proteins
Publisher
MDPI AG
Type
journal article