Curcumin Suppresses In Vitro Proliferation and Invasion of Human Prostate Cancer Stem Cells by Modulating DLK1-DIO3 Imprinted Gene Cluster MicroRNAs

Genet Test Mol Biomarkers. 2018 Jan;22(1):43-50. doi: 10.1089/gtmb.2017.0179. Epub 2017 Nov 27.

Abstract

Aims: Curcumin can suppress human prostate cancer (HuPCa) cell proliferation and invasion. However, it is not known whether curcumin can inhibit HuPCa stem cell (HuPCaSC) proliferation and invasion.

Materials and methods: We used methyl thiazolyl tetrazolium and Transwell assays to examine the proliferation and invasion of the HuPCaSC lines DU145 and 22Rv1 following curcumin or dimethyl sulfoxide (control) treatment. The microRNA (miRNA) expression levels in the DLK1-DIO3 imprinted genomic region in the cells and in tumor tissues from patients with PCa were examined using microarray and quantitative PCR.

Results: The median inhibitory concentration of curcumin for HuPCa cells significantly inhibited HuPCaSC proliferation and invasion in vitro. The miR-770-5p and miR-1247 expression levels in the DLK1-DIO3 imprinted gene cluster were significantly different between the curcumin-treated and control HuPCaSCs. Overexpression of these positive miRNAs significantly increased the inhibition rates of miR-770-5p- and miR-1247-transfected HuPCaSCs compared to the control miR-Mut-transfected HuPCaSCs. Lastly, low-tumor grade PCa tissues had higher miR-770-5p and miR-1247 expression levels than high-grade tumor tissues.

Conclusions: Curcumin can suppress HuPCaSC proliferation and invasion in vitro by modulating specific miRNAs in the DLK1-DIO3 imprinted gene cluster.

Keywords: DLK1-DIO3 imprinted gene cluster microRNAs; curcumin; human prostate cancer stem cells (HuPCaSCs); proliferation and invasion.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Calcium-Binding Proteins
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Curcumin / pharmacology*
  • Genomic Imprinting / drug effects*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Iodide Peroxidase / genetics*
  • Iodide Peroxidase / metabolism
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Multigene Family
  • Neoplasm Invasiveness
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / pathology
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Calcium-Binding Proteins
  • DLK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • MIRN-770 microRNA, human
  • MIRN1247 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • iodothyronine deiodinase type III
  • Iodide Peroxidase
  • Curcumin