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Open AccessActivation of surrogate death receptor signaling triggers peroxynitrite-dependent execution of cisplatin-resistant cancer cells
Platinum-based drugs remain as the cornerstone of cancer chemotherapy; however, development of multidrug resistance presents a therapeutic challenge. This study aims at understanding the molecular mechanisms u...
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Article
Open AccessSmall molecule sensitization to TRAIL is mediated via nuclear localization, phosphorylation and inhibition of chaperone activity of Hsp27
The small chaperone protein Hsp27 confers resistance to apoptosis, and therefore is an attractive anticancer drug target. We report here a novel mechanism underlying the tumor necrosis factor-related apoptosis...
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Open AccessA novel Osmium-based compound targets the mitochondria and triggers ROS-dependent apoptosis in colon carcinoma
Engagement of the mitochondrial-death amplification pathway is an essential component in chemotherapeutic execution of cancer cells. Therefore, identification of mitochondria-targeting agents has become an att...
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Article
Open AccessDeciphering the signaling networks underlying simvastatin-induced apoptosis in human cancer cells: evidence for non-canonical activation of RhoA and Rac1 GTPases
Although statins are known to inhibit proliferation and induce death in a number of cancer cell types, the mechanisms through which downregulation of the mevalonate (MVA) pathway activates death signaling rema...
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Article
Erratum: Bcl-2 induces pro-oxidant state by engaging mitochondrial respiration in tumor cells
Correction to: Cell Death and Differentiation (2007) 14:1617–1627; doi:10.1038/sj.cdd.4402165 In Figure S1b of the Supplementary Figures, the wrong actin blot was used as a loading control, which did not corre...
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Open AccessModulation of Wnt/β-catenin signaling and proliferation by a ferrous iron chelator with therapeutic efficacy in genetically engineered mouse models of cancer
Using a screen for Wnt/β-catenin inhibitors, a family of 8-hydroxyquinolone derivatives with in vivo anti-cancer properties was identified. Analysis of microarray data for the lead compound N-((8-hydroxy-7-quinol...
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Article
Involvement of cytochrome c oxidase subunits Va and Vb in the regulation of cancer cell metabolism by Bcl-2
Bcl-2 has been shown to promote survival of cancer cells by maintaining a slight pro-oxidant state through elevated mitochondrial respiration during basal conditions. On oxidative stress, Bcl-2 moderates mitoc...
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Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes
Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases. Thus, the in-depth investigation of cell death and its mechanisms constitutes a fo...
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Article
Big wheel keeps on turning: apoptosome regulation and its role in chemoresistance
Apoptosis, a form of programmed cell death, enables organisms to maintain tissue homeostasis through deletion of extraneous cells and also serves as a means to eliminate potentially harmful cells. Numerous str...
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Article
LY303511 amplifies TRAIL-induced apoptosis in tumor cells by enhancing DR5 oligomerization, DISC assembly, and mitochondrial permeabilization
Certain classes of tumor cells respond favorably to TRAIL due to the presence of cell surface death receptors DR4 and DR5. Despite this preferential sensitivity, resistance to TRAIL remains a clinical problem ...
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Article
Oxidative repression of NHE1 gene expression involves iron-mediated caspase activity
The mechanism of Na+/H+ exchanger 1 (NHE1) gene repression upon exposure of cells to non-apoptotic concentrations of hydrogen peroxide (H2O2) was investigated. We show that continuous presence of H2O2 was not req...
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Article
Bcl-2 induces pro-oxidant state by engaging mitochondrial respiration in tumor cells
Mitochondrial respiration, the key process behind cellular energy production, is critical for cell proliferation, growth and survival. However, the regulation of mitochondrial respiratory function in tumor cel...
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Article
Reactive oxygen species-mediated regulation of the Na+–H+ exchanger 1 gene expression connects intracellular redox status with cells' sensitivity to death triggers
We have previously demonstrated that a slight increase in intracellular superoxide (O2•−) anion confers resistance to death stimuli. Using pharmacological and molecular approaches to manipulate intracellular O2•−
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Decrease in intracellular superoxide sensitizes Bcl-2-overexpressing tumor cells to receptor and drug-induced apoptosis independent of the mitochondria
At least two mechanisms of early cytosolic acidification during apoptotic signaling have been described, one that involves caspase 8 activation downstream of receptor ligation and another dependent on mitochon...