ArticleGastroenterology2012
4-hydroxy-2-nonenal mediates genotoxicity and bystander effects caused by Enterococcus faecalis-infected macrophages.
Article in Gastroenterology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 139 citations in OpenAlex.
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- Gut Microbiota and Colorectal Cancer: A Balance Between Risk and Protection.International journal of molecular sciences · 2025Review
- Advances in Fecal Microbiota Transplantation for Gut Dysbiosis-Related Diseases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Tryptic oncopeptide secreted from the gut bacterium Cronobacter malonaticus PO3 promotes colorectal cancer.Scientific reports · 2025Article
- [Research progress of aldehyde dehydrogenase type 2 in head and neck malignant tumors].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2025Review
- Clinical Detection and Management of Colorectal Cancer Concerning the Gut Microbiome.Scientifica · 2025Review
- Tumor-associated macrophages in colon cancer immunotherapy: mechanisms, natural product interventions, and microenvironment remodeling.Frontiers in immunology · 2025Review
- Study of Microbiota Associated to Early Tumors Can Shed Light on Colon Carcinogenesis.International journal of molecular sciences · 2024Review
- Beyond Tumor Borders: Intratumoral Microbiome Effects on Tumor Behavior and Therapeutic Responses.Immune network · 2024Review
- Role of Gut Microbiota in Predisposition to Colon Cancer: A Narrative Review.Indian journal of microbiology · 2024Review
- Calcium-rich dairy matrix protects better than mineral calcium against colonic luminal haem-induced alterations in male rats.NPJ science of food · 2024Article
- Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsEnterococcus faecalis is a human intestinal commensal that produces extracellular superoxide and promotes chromosome instability via macrophage-induced bystander effects. We investigated the ability of 4-hydroxy-2-nonenal (4-HNE), a diffusible breakdown product of ω-6 polyunsaturated fatty acids, to mediate these effects.
methods4-HNE was purified from E faecalis-infected macrophages; its genotoxicity was assessed in human colon cancer (HCT116) and primary murine colon epithelial (YAMC) cell lines.
results4-HNE induced G(2)-M cell cycle arrest, led to formation γH2AX foci, and disrupted the mitotic spindle in both cell lines. Binucleate tetraploid cells that formed after incubation with 4-HNE were associated with the activation of stathmin and microtubule catastrophe. Silencing glutathione S-transferase α4, a scavenger of 4-HNE, increased the susceptibility of epithelial cells to 4-HNE-induced genotoxicity. Interleukin-10 knockout mice colonized with superoxide-producing E faecalis developed inflammation and colorectal cancer, whereas colonization with a superoxide-deficient strain resulted in inflammation but not cancer. 4-HNE-protein adducts were found in the lamina propria and macrophages in areas of colorectal inflammation.
conclusions4-HNE can act as an autochthonous mitotic spindle poison in normal colonic epithelial and colon cancer cells. This finding links the macrophage-induced bystander effects to colorectal carcinogenesis.
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