Depletion of Neuroguidin/CANu1 sensitizes human osteosarcoma U2OS cells to doxorubicin

BMB Rep. 2011 Jan;44(1):46-51. doi: 10.5483/BMBRep.2011.44.1.46.

Abstract

Osteosarcoma is a primary bone cancer which occurs mainly in children. Neuroguidin/CANu1 is a nucleolar protein involved in the maintenance of ribosomal structure. In this study, we investigated the effect of Neuroguidin/CANu1 depletion on the response of osteosarcoma cells to doxorubicin. In normal circumstances, Neuroguidin/CANu1 is localized at nucleoli, which translocates to nuclear foci in the presence of doxorubicin. shRNA knockdown of Neuroguidin/CANu1 did not affect cell viability in the absence of doxorubicin, but led to enhanced cytotoxicity in doxorubicin-treated cells. Doxorubicin increased the population of apoptotic cells by 3-fold in Neuroguidin/CANu1-depleted cells compared to that in control cells. Depletion of Neuroguidin/CANu1 mRNA induced the expression of p21 and the cleavage of PARP, leading to increased caspase-3/7 activity. Together, these results suggest that Neuroguidin/CANu1 is required for maintaining cellular homeostasis and may contribute to the improved efficiency of chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / therapeutic use*
  • Antibiotics, Antineoplastic / toxicity
  • Bone Neoplasms / drug therapy*
  • Caspase 3 / metabolism
  • Caspase 7 / metabolism
  • Cell Line, Tumor
  • Cell Survival
  • Doxorubicin / therapeutic use*
  • Doxorubicin / toxicity
  • Humans
  • Neurogranin / genetics
  • Neurogranin / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Osteosarcoma / drug therapy*
  • Poly(ADP-ribose) Polymerases / genetics
  • Poly(ADP-ribose) Polymerases / metabolism
  • RNA Interference
  • RNA, Small Interfering
  • RNA-Binding Proteins

Substances

  • Antibiotics, Antineoplastic
  • NGDN protein, human
  • Nuclear Proteins
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Neurogranin
  • Doxorubicin
  • Poly(ADP-ribose) Polymerases
  • Caspase 3
  • Caspase 7