Inhibition of arginine ADP-ribosyltransferase 1 reduces the expression of poly(ADP-ribose) polymerase-1 in colon carcinoma

Int J Mol Med. 2013 Jul;32(1):130-6. doi: 10.3892/ijmm.2013.1370. Epub 2013 May 8.

Abstract

Poly(ADP-ribose) polymerase-1 (PARP-1) which mediates poly-ADP-ribosylation, has been extensively investigated in carcinoma compared to arginine ADP-ribosyltransferase 1 (ART1), which mediates mono‑ADP‑ribosylation. Previous studies have demonstrated that these enzymes promote proliferation and tumor development in colon carcinoma. However, whether there is any association between PARP-1 and ATR1 in colon carcinoma, remains unelucidated. In this study, using immunohistochemical analysis, we detected a higher expression of PARP-1 and ART1 in 63 samples from patients with colon carcinoma compared to 10 samples of normal colonic mucosa; our results revealed a positive correlation between the expression of PARP-1 and ART1 in the 63 human colon carcinoma tissue samples. To determine the correlation between PARP-1 and ART1, inhibitors of PARP-1 and ART1 and lentivirus vector‑mediated ART1 short‑hairpin RNA (shRNA) were used to culture CT26 murine colon adenocarcinoma cells separately. Using double‑label immunofluorescence assay, we detected the expression of PARP-1 in the CT26 cells, which was decreased following treatment with 5‑aminoisoquinolinone (5-AIQ, a PARP-1 inhibitor) or meta‑iodobenzylguanidine (MIBG, an ART1 inhibitor). However, the expression of ART1 only decreased when the CT26 cells were treated with MIBG. Furthermore, our results demonstrated that silencing ART1 inhibited PARP‑1 expression by decreasing the expression of nuclear factor-κB (NF-κB), inhibiting ras homolog A (RhoA). Hence, our data demonstrate the positive correlation between ART1 and PARP-1; the inhibition of ART1 activity downregulates PARP-1 expression by decreasing the activity of NF-κB in CT26 colon carcinoma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Iodobenzylguanidine / pharmacology
  • ADP Ribose Transferases / antagonists & inhibitors*
  • ADP Ribose Transferases / genetics
  • ADP Ribose Transferases / metabolism
  • Cell Line, Tumor
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / metabolism*
  • GPI-Linked Proteins / antagonists & inhibitors
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Gene Expression Regulation, Neoplastic* / drug effects
  • Gene Knockdown Techniques
  • Gene Silencing
  • Humans
  • Intestinal Mucosa / metabolism
  • Isoquinolines / pharmacology
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / genetics*
  • Poly(ADP-ribose) Polymerases / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism

Substances

  • 5-aminoisoquinolinone
  • GPI-Linked Proteins
  • Isoquinolines
  • NF-kappa B
  • RNA, Small Interfering
  • 3-Iodobenzylguanidine
  • ADP Ribose Transferases
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • ART1 protein, human