ArticleInfection and immunity2009
Antiapoptotic proteins Bcl-2 and Bcl-XL inhibit Clostridium difficile toxin A-induced cell death in human epithelial cells.
Article in Infection and immunity, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Inhibitory effects of Levilactobacillus brevis IBRC-M10790 on apoptosis and inflammation induced by Clostridioides difficile culture supernatant in vitro.Scientific reports · 2025Article
- Mechanisms ofFrontiers in cellular and infection microbiology · 2025Review
- Exploring the Toxin-Mediated Mechanisms inMicroorganisms · 2024Review
- Review
- A leaky human colon model reveals uncoupled apical/basal cytotoxicity in earlyAmerican journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Curcumin and capsaicin regulate apoptosis and alleviate intestinal inflammation induced by Clostridioides difficile in vitro.Annals of clinical microbiology and antimicrobials · 2022Article
- Clostridioides difficile toxin B alone and with pro-inflammatory cytokines induces apoptosis in enteric glial cells by activating three different signalling pathways mediated by caspases, calpains and cathepsin B.Cellular and molecular life sciences : CMLS · 2022Article
- Mechanism of inhibition of Shiga-toxigenicCell death discovery · 2018Article
- Apoptosis of intestinal epithelial cells restricts Clostridium difficile infection in a model of pseudomembranous colitis.Nature communications · 2018Article
- The role of toxins in Clostridium difficile infection.FEMS microbiology reviews · 2017Review
- Clostridium difficile Toxins TcdA and TcdB Cause Colonic Tissue Damage by Distinct Mechanisms.Infection and immunity · 2016Article
- Clostridium difficile infection: molecular pathogenesis and novel therapeutics.Expert review of anti-infective therapy · 2014Review
- The P2Y6 receptor mediates Clostridium difficile toxin-induced CXCL8/IL-8 production and intestinal epithelial barrier dysfunction.PloS one · 2013Article
- Nanoparticle delivery of a peptide targeting EGFR signaling.Journal of controlled release : official journal of the Controlled Release Society · 2012Article
- Clostridium difficile Toxin B causes epithelial cell necrosis through an autoprocessing-independent mechanism.PLoS pathogens · 2012Article
- Yersinia enterocolitica YopT and Clostridium difficile toxin B induce expression of GILZ in epithelial cells.PloS one · 2012Article
- Prophage-stimulated toxin production in Clostridium difficile NAP1/027 lysogens.Journal of bacteriology · 2011Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It has been well established that Clostridium difficile toxin A (TcdA) induces cell death in human epithelial cells. However, the mechanism of TcdA-induced cell death remains to be fully characterized. Here, we show that TcdA induces dose-dependent cell death in ovarian carcinoma and colonic carcinoma cell lines. TcdA-mediated cell death, as well as caspase 8 and caspase 3 activation, were specifically abrogated by anti-toxin antibodies. Although caspase 8 and caspase 3 were activated by TcdA in OVCAR3 ovarian carcinoma and T84 colonic cancer cells, pancaspase and caspase 8, 3, and 9 inhibitors did not block TcdA-induced cell death. In contrast, tumor necrosis factor-related apoptosis-inducing ligand-induced cell death was nearly completely blocked by caspase inhibitors in OVCAR3 cells. In these cells, TcdA induces the mitochondrial pathway of apoptosis, as demonstrated by changes in mitochondrial outer membrane permeabilization (MOMP). Furthermore, overexpression of the antiapoptotic proteins Bcl-2 and Bcl-X(L) significantly inhibited TcdA-induced cell death, as well as TcdA-induced MOMP. Conversely, small interfering RNA-mediated inhibition of Bcl-X(L) in TcdA-resistant SKOV3ip1 cells enhanced TcdA-induced cell death. Overexpression of the antiapoptotic proteins Bcl-2 and Bcl-X(L) in T84 cells also inhibited TcdA-induced cell death. Altogether, our data demonstrate that TcdA induces cell death in both ovarian and colonic cancer cells preferentially via the mitochondrial pathway of apoptosis by a death receptor-independent and a caspase-independent mechanism. This process is regulated by antiapoptotic members of the Bcl-2 family.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.