Valproic Acid Induces Decreased Expression of H19 Promoting Cell Apoptosis in A549 Cells

DNA Cell Biol. 2017 Jun;36(6):428-435. doi: 10.1089/dna.2016.3542. Epub 2017 Mar 22.

Abstract

It has been suggested that the imprinted gene, H19, plays a crucial role in the development of cancer. In the present study, we attempted to treat the abnormal expression and methylation status of H19 in A549 cells using valproic acid (VPA), ascorbic acid (Vc), and 5-aza-Cytidine (5-Aza). The results suggested that VPA administration could alter the expression pattern of H19, while the hypomethylation status of H19 DMR was unchanged. Furthermore, overexpression of HDAC1 and DNMT1 was associated with decreased expression of H19 in VPA-treated cells. Western blot results showed that the expression of p53 protein was increased following treatment with VPA. In addition, we also investigated cellular apoptosis and the cell cycle of treated cells. Flow cytometry data indicated that VPA could increase the occurrence of cell apoptosis in A549 cells. Taken together, our results suggest that H19 expression was suppressed by VPA through HDAC1 and DNMT1 and decreased H19 expression correlated with cell apoptosis in A549 cells.

Keywords: DNA methylation; DNMT1; H19; HDAC1; VPA; cancer.

MeSH terms

  • A549 Cells
  • Apoptosis / drug effects*
  • Cell Cycle / drug effects
  • DNA Methylation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • RNA, Long Noncoding / genetics*
  • Valproic Acid / pharmacology*

Substances

  • H19 long non-coding RNA
  • RNA, Long Noncoding
  • Valproic Acid