Knockdown of the DNA repair and redox signaling protein Ape1/Ref-1 blocks ovarian cancer cell and tumor growth

Melissa L. Fishel, Ying He, April M. Reed, Helen Chin-Sinex, Gary D. Hutchins, Marc S. Mendonca, Mark R. Kelley

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Apurinic endonuclease 1/redox effector factor-1 (Ape1/Ref-1 or Ape1) is an essential protein with two distinct functions. It is a DNA repair enzyme in the base excision repair (BER) pathway and a reduction-oxidation (redox) signaling factor maintaining transcription factors in an active reduced state. Our laboratory previously demonstrated that Ape1 is overexpressed in ovarian cancer and potentially contributes to resistance. Therefore, we utilized siRNA technology to knockdown protein levels of Ape1 in ovarian cancer cell line, SKOV-3x. Knocking Ape1 down had dramatic effects on cell growth in vitro but was not due to an increase in apoptosis and at least partially due to an extension in transit time through S-phase. Similarly, human ovarian tumor xenografts with reduced levels of Ape1 protein demonstrated a dramatic reduction in tumor volume (p < 0.01) and also statistically significant (p = 0.02) differences in 18F-fluorodeoxyglucose (FDG) uptake indicating reduced glucose metabolism and cellular proliferation. Ape1's role in DNA repair and redox signaling is important to our basic understanding of ovarian cancer cell growth and these findings strongly support Ape1 as a therapeutic target.

Original languageEnglish (US)
Pages (from-to)177-186
Number of pages10
JournalDNA Repair
Volume7
Issue number2
DOIs
StatePublished - Feb 1 2008

Fingerprint

DNA Repair
Ovarian Neoplasms
Tumors
Repair
Cells
Oxidation
DNA
Cell growth
Growth
DNA-(Apurinic or Apyrimidinic Site) Lyase
DNA Repair Enzymes
Neoplasms
Proteins
Fluorodeoxyglucose F18
Tumor Burden
S Phase
Heterografts
Small Interfering RNA
Transcription Factors
Cell Proliferation

Keywords

  • Apurinic endocuclease1/redox effector factor-1
  • Base excision repair
  • Cell cycle
  • Ovarian cancer
  • Tumor xenograft

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Knockdown of the DNA repair and redox signaling protein Ape1/Ref-1 blocks ovarian cancer cell and tumor growth. / Fishel, Melissa L.; He, Ying; Reed, April M.; Chin-Sinex, Helen; Hutchins, Gary D.; Mendonca, Marc S.; Kelley, Mark R.

In: DNA Repair, Vol. 7, No. 2, 01.02.2008, p. 177-186.

Research output: Contribution to journalArticle

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