Role of mitochondrial membrane permeabilization in apoptosis and cancer

Henry-Mowatt, Judith; Dive, Caroline; Martinou, Jean‐Claude; James, Dominic I.

doi:10.1038/sj.onc.1207534

Cited by 257 publications

(155 citation statements)

References 128 publications

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“…A large number of such assays have been used and most of them are reliable. However, (1) cells having sub-G 1 DNA content have been assumed to be apoptotic (Chan et al, 2003;Jazirehi et al, 2003), but various types of cell fragments also may have a sub-G 1 DNA content, and we demonstrate herein that three types of necrotic cell preparations have large numbers of cells with sub-G 1 DNA; (2) similarly, although apoptotic cells lose mitochondrial membrane potential (Darzynkiewicz et al, 2001) and although the mitochondrial membrane is a major focus of apoptotic pathways (Green, 2003;Henry-Mowatt et al, 2004), we show that necrotic cells also lose mitochondrial membrane potential; (3) subcellular fragments can potentially interfere with assays such as annexin V staining. Apoptosis and other types of cell death usually generate subcellular fragments, and these may be mistaken for apoptotic cells; (4) cell damage owing to irradiation causes an increase in nonspecific Ab binding (to viable, nonapoptotic cells), which can lead to false conclusions regarding Ab specificity if negative control Abs are not tested; and (5) Ab binding can induce tight aggregation of cells, especially if a secondary Ab is included.…”

supporting

confidence: 57%

Apoptosis assays with lymphoma cell lines: problems and pitfalls

Mattes

2007

Br J Cancer

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Much attention has been focused on the manner in which tumour cells die after treatment with cytotoxic agents. The basic question is whether cells die via apoptosis or via direct damage from the toxic agent. Various assays have been used to make this distinction. However, we show herein that some of the widely used assays for apoptosis do not in fact distinguish between apoptosis and other forms of cell death. More specifically: (1) A sub-G 1 DNA content, identified by propidium iodide staining, does not distinguish between apoptotic and necrotic cells; (2) loss of mitochondrial membrane potential does not distinguish between apoptotic and necrotic cells, unless combined with an assay for an intact cell membrane; (3) subcellular fragments that arise from dead cells or from apoptotic bodies can interfere with some assays for apoptosis such as annexin V staining, as they may be close to the size of intact cells, making it difficult to decide where to set the size threshold; (4) irradiated cells display a large increase in nonspecific Ab binding. This may be partly due to an increase in cell size, but, regardless of the cause, it can lead to a mistaken conclusion that there is an increase in a particular antigen if appropriate control reagents are not tested; and (5) experiments utilising Ab crosslinking have neglected the role of cell aggregation, which can cause multiple problems including death from mechanical stress when cells are handled. Consideration of these factors will improve our ability to determine the mode of cell death.

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supporting

confidence: 57%

Apoptosis assays with lymphoma cell lines: problems and pitfalls

Mattes

2007

Br J Cancer

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“…The mechanisms regulating the release of specific mitochondrial proteins during cell death are not completely understood (Donovan and Cotter, 2004;Henry-Mowatt et al, 2004;Saelens et al, 2004). Our data showed that A3D8 treatment induced loss of DCm and AIF release from mitochondria without cytochrome c release.…”

Section: Cd44-induced Cell Death In Erythroleukemia Cellsmentioning

confidence: 71%

“…Key events in classic apoptosis as well as in other forms of cell death are the disruption of mitochondrial function and the release of apoptogenic proteins from the intermembrane space (IMS) of mitochondria (Henry-Mowatt et al, 2004;Saelens et al, 2004). Although the process of the mitochondrial outer membrane permeabilization (MOMP) is mainly controlled by the members of the Bcl-2 family, the exact mechanisms responsible of this process remain controversial (Donovan and Cotter, 2004).…”

Section: Introductionmentioning

confidence: 99%

CD44 ligation induces caspase-independent cell death via a novel calpain/AIF pathway in human erythroleukemia cells

et al. 2006

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Ligation of the cell surface molecule CD44 by anti-CD44 monoclonal antibodies (mAbs) has been shown to induce cell differentiation, cell growth inhibition and in some cases, apoptosis in myeloid leukemic cells. We report, herein, that exposure of human erythroleukemic HEL cells to the anti-CD44 mAb A3D8 resulted in cell growth inhibition followed by caspase-independent apoptosis-like cell death. This process was associated with the disruption of mitochondrial membrane potential (DWm), the mitochondrial release of apoptosis-inducing factor (AIF), but not of cytochrome c, and the nuclear translocation of AIF. All these effects including cell death, loss of mitochondrial DWm and AIF release were blocked by pretreatment with the poly (ADP-ribose) polymerase inhibitor isoquinoline. A significant protection against cell death was also observed by using small interfering RNA for AIF. Moreover, we show that calpain protease was activated before the appearance of apoptosis, and that calpain inhibitors or transfection of calpain-siRNA decrease A3D8-induced cell death, and block AIF release. These data suggest that CD44 ligation triggers a novel caspaseindependent cell death pathway via calpain-dependent AIF release in erythroleukemic HEL cells.

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“…Two major apoptotic signaling pathways have been identified: the death receptor-mediated (extrinsic) pathway and the mitochondrial (intrinsic) pathway (Ashkenazi and Dixit, 1998;Kroemer and Reed, 2000;Gupta, 2003;Debatin and Krammer, 2004;Henry-Mowatt et al, 2004). The relative contribution of death receptor versus mitochondrial pathways in apoptosis reflects the existence of two different cell types.…”

Section: Introductionmentioning

confidence: 99%

“…Bax and Bak proteins contain three BH domains and are localized in the cytosol and mitochondrial membrane. Other proapoptotic proteins containing a single BH domain serve either to inactivate antiapoptotic proteins or activate Bax or Bak (Gupta, 2003;Henry-Mowatt et al, 2004;Saelens et al, 2004). Bad is a BH3-only protein that links survival signals to the mitochondrial cell death machinery (Zha et al, 1996;Korsmeyer et al, 1999;Datta et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Methylseleninic acid sensitizes prostate cancer cells to TRAIL-mediated apoptosis

et al. 2005

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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytotoxic agent that preferentially induces apoptosis in a variety of human cancer cells. Unfortunately, some tumor cells remain resistant to TRAIL. Therefore, agents that sensitize malignant cells to TRAIL-mediated cell death might be of particular importance for the development of novel antitumor therapeutic regimens. Recent studies establish a critical role of selenium in prostate cancer prevention in vitro and in vivo. Here, we demonstrate that concomitant administration of TRAIL and methylseleninic acid (MSA) produces synergistic effects on the induction of apoptosis in androgen-dependent LNCaP and androgen-independent DU-145 prostate cancer cells. MSA rapidly and specifically downregulates expression of the cellular FLICE inhibitory protein, a negative regulator of death receptor signaling. In addition, we demonstrate that the synergistic effects of MSA and TRAIL result from the activation of the mitochondrial pathway-mediated amplification loop. Addition of MSA effectively blocked TRAIL-mediated BAD phosphorylation at Ser112 and Ser136 in DU-145 cells and was accompanied by induction of the mitochondrial permeability transition and release of apoptogenic cytochrome c and Smac/DIABLO proteins from the mitochondria and into the cytosol. These results suggest that selenium-based dietary compounds may help to overcome resistance to TRAIL-mediated apoptosis in prostate cancer cells.

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Role of mitochondrial membrane permeabilization in apoptosis and cancer

Cited by 257 publications

References 128 publications

Apoptosis assays with lymphoma cell lines: problems and pitfalls

Apoptosis assays with lymphoma cell lines: problems and pitfalls

CD44 ligation induces caspase-independent cell death via a novel calpain/AIF pathway in human erythroleukemia cells

Methylseleninic acid sensitizes prostate cancer cells to TRAIL-mediated apoptosis

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