Apoptosis-Inducing Factor and Colon Cancer

Universidad Autonoma de Guerrero, UIEM, Chilpancingo, Guerrero, Mexico.
Journal of Surgical Research (Impact Factor: 1.94). 12/2007; 151(1):163-70. DOI: 10.1016/j.jss.2007.05.020
Source: PubMed


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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    • "Nuclear relocation of EndoG and AIF induces DNA fragmentation and apoptotic cell death. However, the release of EndoG and AIF from the mitochondria in response to proapoptotic stimuli also occurs in a caspase-dependent manner [14] [15] [16]. Moreover, previous studies have shown that reactive oxygen species (ROS) and disruption of the MMP contribute to apoptosis induced by chemotherapeutic agents [17] [18]. "
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    ABSTRACT: The aim of this study was to evaluate the beneficial effects of Schisandrae semen essential oil (SSeo) on apoptosis events and the mechanisms associated with these effects in human leukemia U937 cells. The treatment of U937 cells with SSeo significantly inhibited survival and induced apoptosis. Schisandrae semen essential oil treatment increased the levels of death receptors and Fas, and activated caspases accompanied by proteolytic degradation of poly(ADP-ribose)-polymerase, which was associated with the downregulation of members of the inhibitor of apoptosis protein family protein expression; however, a pan-caspase inhibitor reversed SSeo-induced apoptosis. Treating the cells with SSeo also caused truncation of Bid, translocation of proapoptotic Bax to the mitochondria, and loss of mitochondrial membrane permeabilization, thereby inducing the release of cytochrome c into the cytosol. Subsequently, SSeo upregulated the translocation of mitochondrial apoptogenic factors, such as endonuclease G and apoptosis-inducing factor, into the nucleus during the apoptotic process. Notably, SSeo immediately increased the generation of intracellular reactive oxygen species (ROS); however, pretreatment with N-acetylcysteine, a common ROS quencher, almost completely blocked SSeo-induced apoptosis. Taken together, these findings indicate that SSeo caused ROS- and caspase-dependent cell death involving mitochondrial dysfunction and nuclear translocation of mitochondrial proapoptosis proteins. Based on our data, the consumption of Schisandrae semen or its essential oil is a good natural therapeutic agent for anticancer activity and regression. Copyright © 2015. Published by Elsevier Inc.
    Nutrition research 07/2015; 35(10). DOI:10.1016/j.nutres.2015.06.016 · 2.47 Impact Factor
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    • "AIFM1, apoptosis-inducing factor, mitochondrion associated 1 (also abbreviated as AIF), is a flavoprotein, which is involved in initiating caspase-independent pathway of apoptosis [41] [42]. AIF negative tumors have poorer chemotherapeutic prognosis and survival ratio [43] [44] [45]. Increased expression of AIF in HER2 overexpressing human breast cancer cells is suggestive of apoptosis activation. "
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    ABSTRACT: Unlabelled: Molecular classification of breast cancer is based, in part, on the presence or absence of amplification of the human epidermal growth factor receptor 2 (ERBB2) gene, which leads to HER2 protein overproduction. While the presence of the overexpressed HER2 protein is a necessary precondition for sensitivity to anti-HER2 therapies, many patients develop resistance. Thus, identification of the downstream effectors of this pathway will help in understanding mechanism(s) of chemoresistance and further, the identified molecules themselves may have the potential to be used as therapeutic targets. In this work, we studied the proteomic changes that accompany the HER2 gene amplification to identify potential new therapeutic targets and biomarkers. We analyzed bio-triplicate proteome samples extracted from wild-type MCF-7 human breast cancer cells and their isogenic stably overexpressing HER2 (amplified) transfectants. In total, 2455 unique proteins were quantified with 1278 of them differentially expressed in HER2 normal and HER2 overexpressing MCF-7 cells. Select biomarker candidates of particular interest were validated by western blotting, and evaluated for clinical relevance by the immunohistochemical assessment of protein abundance in breast tumor biopsies. HER2 transfection produced marked changes in proteins related to multiple aspects of cancer biology, and the identified expression patterns were recapitulated in the clinical samples. Biological significance: Breast cancer is a major cause of death in women. Molecular classification of breast cancer is based, in part, on the presence or absence of amplification of the human epidermal growth factor receptor 2 (ERBB2) gene, which leads to HER2 protein overproduction that triggers intracellular signaling events that drive proliferation, invasion, metastases, and resistance to apoptosis. While the presence of the overexpressed HER2 gene product, HER2 protein, is a necessary precondition for sensitivity to the therapeutic monoclonal antibody trastuzumab, the downstream effects of HER2 protein overexpression are incompletely understood. In this work, we applied quantitative proteomics to identify proteomic changes accompanying ERBB2 gene amplification. The significance of this work includes 1) identification of new biomarkers associated with the HER2 phenotype, 2) measurement of the magnitude of the proteomic changes triggered by the amplification of this single gene, and 3) better understanding of the downstream biological changes triggered by HER2 overexpression.
    Journal of proteomics 07/2013; 91. DOI:10.1016/j.jprot.2013.06.034 · 3.89 Impact Factor
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    • "Since cell death could be divided into apoptosis or necrosis. Apoptosis is more favourable than necrosis because it is a programmed cell death that does not trigger inflammatory responses [13]. In AO/PI staining, DNA-binding dye acridine orange (AO) and propidium iodide (PI) were used for morphological detection of apoptotic and necrotic cells. "
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    ABSTRACT: Kenaf ( Hibiscus cannabinus ) from the family Malvaceae, is a valuable fiber plant native to India and Africa and is currently planted as the fourth commercial crop in Malaysia. Kenaf seed oil contains alpha-linolenic acid, phytosterol such as β -sitosterol, vitamin E, and other antioxidants with chemopreventive properties. Kenaf seeds oil (KSO) was from supercritical carbon dioxide extraction fluid (SFE) at 9 different permutations of parameters based on range of pressures from 200 to 600 bars and temperature from 40 to 80°C. They were 200/40, 200/60, 200/80, 400/40, 400/60, 400/80, 600/40, 600/60, and 600/80. Extraction from 9 parameters of KSO-SFE was screened for cytotoxicity towards human colorectal cancer cell lines (HT29) and mouse embryonic fibroblast (NIH/3T3) cell lines using MTS assay. KSO-SFE at 600/40 showed the strongest cytotoxicity towards HT29 with IC 50 of 200 µg/mL. The IC 50 for NIH/3T3 was not detected even at highest concentration employed. Cell cycle analysis showed a significant increase in the accumulation of KSO-SFE-treated cells at sub-G1 phase, indicating the induction of apoptosis by KSO-SFE. Further apoptosis induction was confirmed by Annexin V/PI and AO/PI staining.
    Evidence-based Complementary and Alternative Medicine 03/2013; 2013(3):549705. DOI:10.1155/2013/549705 · 1.88 Impact Factor
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