Going ape as an approach to cancer therapeutics

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

The DNA base excision repair (BER) pathway repairs alkylation and oxidative DNA damage caused by endogenous and exogenous agents, including chemotherapeutic agents. Upon removal of the damaged base AP endonuclease 1 (Ape1), a critical component of the pathway cleaves the abasic site to facilitate repair. Ape1 is a multifunctional protein which plays a role not only in DNA repair but it also functions as a reduction-oxidation factor, known as Ref-1 in the literature, to increase the DNA binding ability of several transcription factors involved in different growth signaling pathways. Elevated levels of Ape1 have been linked to resistance to chemotherapy, poor prognosis, and poor survival. Reducing the amount of Ape1 protein in cancer cells and tumors using RNA interference and anti-sense oligonucleotide technology sensitizes mammalian tumor cells to a variety of laboratory and chemotherapeutic agents. Therefore, selective inhibition of Ape1's DNA repair activity is a promising avenue to develop novel cancer therapeutics.

Original languageEnglish
Pages (from-to)651-667
Number of pages17
JournalAntioxidants and Redox Signaling
Volume11
Issue number3
DOIs
StatePublished - Mar 1 2009

Fingerprint

DNA-(Apurinic or Apyrimidinic Site) Lyase
Hominidae
Transcription Factor AP-1
Repair
DNA Repair
DNA
Neoplasms
Tumors
Critical Pathways
Cells
Antisense Oligonucleotides
Alkylation
Therapeutics
RNA Interference
Chemotherapy
DNA Damage
Proteins
Transcription Factors
Technology
Drug Therapy

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Physiology
  • Clinical Biochemistry
  • Medicine(all)

Cite this

Going ape as an approach to cancer therapeutics. / Bapat, Aditi; Fishel, Melissa; Kelley, Mark.

In: Antioxidants and Redox Signaling, Vol. 11, No. 3, 01.03.2009, p. 651-667.

Research output: Contribution to journalArticle

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