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Int. J. Mol. Sci. 2015, 16(10), 23994-24010; doi:10.3390/ijms161023994

Increased Histone Deacetylase Activity Involved in the Suppressed Invasion of Cancer Cells Survived from ALA-Mediated Photodynamic Treatment

1
Department of Biochemical Science and Technology, National Taiwan University, Taipei 106, Taiwan
2
Department of Neurology, National Taiwan University Hospital, 7, Chung-Shan South Road, Taipei 100, Taiwan
*
Authors to whom correspondence should be addressed.
Academic Editor: Michael R. Hamblin
Received: 22 August 2015 / Accepted: 25 September 2015 / Published: 10 October 2015
(This article belongs to the Special Issue Advances in Photodynamic Therapy)
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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. View Full-Text
Keywords: histone acetylation; histone deacetylase; invasion; mitochondria; metalloproteinase 9; paternally expressed gene 1 histone acetylation; histone deacetylase; invasion; mitochondria; metalloproteinase 9; paternally expressed gene 1
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Li, P.-T.; Tsai, Y.-J.; Lee, M.-J.; Chen, C.-T. Increased Histone Deacetylase Activity Involved in the Suppressed Invasion of Cancer Cells Survived from ALA-Mediated Photodynamic Treatment. Int. J. Mol. Sci. 2015, 16, 23994-24010.

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