Emodin promotes the arrest of human lymphoma Raji cell proliferation through the UHRF1‑DNMT3A‑∆Np73 pathways

Mol Med Rep. 2017 Nov;16(5):6544-6551. doi: 10.3892/mmr.2017.7423. Epub 2017 Sep 5.

Abstract

Emodin is an active constituent found in the roots and rhizomes of numerous Chinese medicinal herbs. It exerts antitumor activity against Dalton's lymphoma in vivo, although the detailed mechanisms by which emodin induces apoptosis remains to be elucidated. The present study aimed to analyze the mechanisms underlying the response to emodin treatment. Using lymphoma Raji cells, an emodin‑induced cell proliferating inhibition model was first established, then flow cytometry, western blotting, reverse transcription‑quantitative polymerase chain reaction and luciferase reporter assay were performed. It was found that emodin decreased the percentage of Raji cell viability, induced apoptosis, and increased the activation of caspase 3, caspase 9 and poly (ADP‑ribose) polymerase through the downregulation of ubiquitin‑like protein containing PHD and RING domains 1 (UHRF1). The emodin‑induced downregulation of UHRF1 led to an increase in the level of DNA methyltransferase 3A, which in turn inhibited the activity of p73 promoter 2 and decreased the levels of NH2‑terminally truncated dominant‑negative p73. The treatment of Raji cells with emodin combined with doxorubicin led increased cell death of Raji cells, indicating that emodin may sensitize Raji cells to doxorubicin‑induced apoptosis.

MeSH terms

  • Apoptosis / drug effects
  • CCAAT-Enhancer-Binding Proteins / metabolism*
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • DNA (Cytosine-5-)-Methyltransferases / metabolism*
  • DNA Methyltransferase 3A
  • Down-Regulation / drug effects
  • Doxorubicin / pharmacology
  • Emodin / pharmacology*
  • Humans
  • Lymphoma / drug therapy*
  • Lymphoma / metabolism
  • Poly(ADP-ribose) Polymerases / metabolism
  • Ubiquitin-Protein Ligases

Substances

  • CCAAT-Enhancer-Binding Proteins
  • DNMT3A protein, human
  • Doxorubicin
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A
  • UHRF1 protein, human
  • Ubiquitin-Protein Ligases
  • Poly(ADP-ribose) Polymerases
  • Caspase 3
  • Caspase 9
  • Emodin