Apoptosis-Inducing Factor and Colon Cancer

Alejandro Millan, Sergio Huerta

Research output: Contribution to journalReview article

60 Scopus citations

Abstract

Programmed cell death is a fundamental requirement for embryogenesis, organ metamorphosis, and tissue homeostasis. Since the vast majority of cytotoxic modalities exert their anti-tumor effects by induction of apoptosis, programmed cell death has emerged as a potential target for cancer treatment at various stages of tumor progression. Immuno-regulation and chemoradiosensitization are potential pathways where insight in apoptotic mechanisms may lead to improvement of chemoradiotherapeutic modalities. The central mediator of the intrinsic pathway of apoptosis is the mitochondrion, in which changes of the outer membrane's permeability cause an outflow of cytochrome c and more than 40 molecules involved in apoptosis. These include Smac/DIABLO, Omi/HTR A2, endonuclease G, and apoptosis inducing factor (AIF). AIF, a 57 kDa mitochondrial oxidoreductase, is released into the cytoplasm and translocates to the nucleus to induce cell death in response to poly-(ADP-ribose) polymerase-1 activation, resulting is DNA fragmentation independent of caspase activation. As a caspase-independent mechanism of apoptosis, AIF may be a potential target for chemoradiotherapeutic intervention in a number of malignancies. The aim of this review is to provide the available evidence of the role AIF in several malignancies with a particular emphasis in colon carcinogenesis.

Original languageEnglish (US)
Pages (from-to)163-170
Number of pages8
JournalJournal of Surgical Research
Volume151
Issue number1
DOIs
StatePublished - Jan 1 2009

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Keywords

  • AIF
  • apoptosis
  • cancer
  • chemotherapy
  • colon cancer
  • mitochondria
  • poly-(ADP-ribose) polymerase-1 (PARP-1)

ASJC Scopus subject areas

  • Surgery

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