Article

Apoptosis-inducing factor and colon cancer

Universidad Autonoma de Guerrero, UIEM, Chilpancingo, Guerrero, Mexico.
Journal of Surgical Research (Impact Factor: 2.12). 12/2007; 151(1):163-70. DOI: 10.1016/j.jss.2007.05.020
Source: PubMed

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.

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    • "Apoptosis, or programmed cell death is a highly regulated process that occurs in almost all living organisms that eliminates unwanted cells. This process occurs in a systematic fashion and is characterized by a sequence of morphological alterations and biochemical changes upon the activation of a series of molecular signaling cascades in cells (Allen et al., 1997; Hu and Kavanagh, 2003; Wang et al., 2005; Millan and Huerta, 2009). Apoptosis is part of a wide array of normal physiological processes and plays an important role in many normal functions of multicellular organisms by allowing the organism to tightly control cell numbers and tissue size in many developmental and physiological settings (Hengartner, 2000; Hu and Kavanagh, 2003). "
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    • "Apoptotic stimulus results in the overexpression of AIFM2 in the cytoplasm that translates into the nucleus. The DNA binds to the amino acid residues in the C-terminal domain of AIFM2 facilitating apoptosis (Alejandro, 2009; Marshall, 2005).The structural features of AIFM2 protein is important for understanding of the protein binding to the DNA. "
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    • "Pancreatic beta cell apoptosis plays a crucial role in the pathogenesis of Type 1 Diabetes mellitus (T1DM) (Atkinson, 2005; Eizirik and Mandrup-Poulsen, 2001; Kim and Lee, 2009). This process is initiated by two main pathways: the " extrinsic " or death receptor and the " intrinsic " or mitochondrial apoptosis pathway (Huerta et al., 2007; Millan and Huerta, 2009). The intrinsic death pathway involves loss of mitochondrial homeostasis, particularly of the outer mitochondrial membrane integrity, and subsequently the release of mitochondrial pro-apoptotic factors including cytochrome c. "
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