Anticancer effects of Escherichia coli-derived outer membrane vesicles against colorectal cancer cells through regulation of apoptosis
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Abstract
Background: Colorectal cancer is one of the deadliest cancers with poor prognosis and limited treatment options. Microbiota and their metabolites, including toxins, have been shown to possess anti-tumor properties. Outer membrane vesicles (OMVs) from Escherichia coli may trigger inflammation in intestinal cells. We aimed to explore the anti-cancer effects of E. coli-derived OMVs on colorectal cancer cells by promoting apoptosis and pyroptosis, particularly through the over-expression of GSDMD in the CT-26 cell line.
Methods: In 2022, five non-replicating probiotic strains of E. coli were obtained from the Histogenotech Company in Tehran, and their OMVs were isolated and characterized. The CT-26 cell line was used to assess cell toxicity and the apoptotic effects of E. coli-derived OMVs. Real-time PCR and western blotting were performed to measure the expression of apoptosis and pyroptosis markers (GSDMD, NLRP3, and ROCK).
Results: The E. coli strains produced nanovesicles (5-200 nm in diameter). OMVs significantly reduced the viability of CT-26 cells and induced apoptosis at a concentration of 10 µg. The expression of GSDMD and NLRP3 was increased, while ROCK expression was downregulated in treated colorectal cells.
Conclusion: E. coli-derived OMVs can trigger inflammatory processes and induce negative effects on colorectal cancer cells. Further research is needed to evaluate their potential for colorectal cancer treatment.
Keywords: E. coli; ; r; Apoptosis; Inflammation
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30. Jin L, Zhang Z, Tan X, et al (2022). Antitumor effect of Escherichia coli-derived outer membrane vesicles on neuroblastoma in vitro and in vivo: Effect of E. coli-OMVs on neuroblastoma. Acta Biochim Biophys Sin (Shanghai), 54(9):1301-1313.
31. Kim OY, Park HT, Dinh NTH, et al (2017). Bacterial outer membrane vesicles suppress tumor by interferon-γ-mediated antitumor response. Nat Commun, 8(1):626.
32. Alizadeh S, Esmaeili A, Omidi Y (2020). Anti-cancer properties of Escherichia coli Nissle 1917 against HT-29 colon cancer cells through regulation of Bax/Bcl-xL and AKT/PTEN signaling pathways. Iran J Basic Med Sci, 23(7):886-893.
33. Yang J, Hwang I, Lee E, et al (2020). Bacterial outer membrane vesicle-mediated cytosolic delivery of flagellin triggers host NLRC4 canonical inflammasome signaling. Front Immunol, 11:581165.
2. Thrift AP, El-Serag HB (2020). Burden of gastric cancer. Clin Gastroenterol Hepatol, 18(3):534-42.
3. Iyadorai T, Mariappan V, Vellasamy KM, et al (2020). Prevalence and association of pks+ Escherichia coli with colorectal cancer in patients at the University Malaya Medical Centre, Malaysia. PLoS One, 15(1):e0228217.
4. Lucas C, Barnich N, Nguyen HTT (2017). Microbiota, inflammation and colorectal cancer. Int J Mol Sci, 18(6):1310.
5. O'keefe SJ (2016). Diet, microorganisms and their metabolites, and colon cancer. Nat Rev Gastroenterol Hepatol, 13(12):691-706.
6. Zitvogel L, Daillère R, Roberti MP, et al (2017). Anticancer effects of the microbiome and its products. Nat Rev Microbiol, 15(8):465-78.
7. Mohammadzadeh N, Kalani BS, Bolori S, et al (2019). Identification of an intestinal microbiota signature associated with hospitalized patients with diarrhea. Acta Microbiol Immunol Hung, 66(2):189-202.
8. Nakkarach A, Foo HL, Song AA-L, et al (2021). Anti-cancer and anti-inflammatory effects elicited by short chain fatty acids produced by Escherichia coli isolated from healthy human gut microbiota. Microb Cell Fact, 20:36.
9. Cañas M-A, Fábrega M-J, Giménez R, et al (2018). Outer membrane vesicles from probiotic and commensal Escherichia coli activate NOD1-mediated immune responses in intestinal epithelial cells. Front Microbiol, 9:498.
10. Bolori S, Shegefti S, Baghaei K, et al (2023). The Effects of Helicobacter pylori‐Derived Outer Membrane Vesicles on Hepatic Stellate Cell Activation and Liver Fibrosis In Vitro. Biomed Res Int, 2023:4848643.
11. Zahmatkesh ME, Jahanbakhsh M, Hoseini N, et al (2022). Effects of exosomes derived from Helicobacter pylori outer membrane vesicle-infected hepatocytes on hepatic stellate cell activation and liver fibrosis induction. Front Cell Infect Microbiol, 12:857570.
12. Shegefti S, Bolori S, Nabavi-Rad A, et al (2023). Helicobacter pylori-derived outer membrane vesicles suppress liver autophagy: A novel mechanism for H. pylori-mediated hepatic disorder. Microb Pathog, 183:106319.
13. Chaudhry G-e-S, Md Akim A, Sung YY, et al (2022). Cancer and apoptosis: The apoptotic activity of plant and marine natural products and their potential as targeted cancer therapeutics. Front Pharmacol, 13:842376.
14. Lowe SW, Lin A W (2000). Apoptosis in cancer. Carcinogenesis, 21(3):485-95.
15. Rizzuto R, Giorgi C, Romagnoli A, Pinton P (2008). Ca2+ signaling, mitochondria and cell death. Curr Mol Med, 8(2):119-30.
16. Watson A (2004). Apoptosis and colorectal cancer. Gut, 53(11):1701-9.
17. Fang Y, Tian S, Pan Y, et al (2020). Pyroptosis: A new frontier in cancer. Biomed Pharmacother, 121:109595.
18. Peng X, Na R, Zhou W, et al (2022). Nuclear translocation of Gasdermin D sensitizes colorectal cancer to chemotherapy in a pyroptosis-independent manner. Oncogene, 41(47):5092-5106.
19. Zhuang Y-P, Zhou H-L, Chen H-B, et al (2023). Gut microbiota interactions with antitumor immunity in colorectal cancer: From understanding to application. Biomed Pharmacother, 165:115040.
20. Sidhu M, van der Poorten D (2017). The gut microbiome. Aust Fam Physician, 46(4):206-11.
21. Wittkopf N, Neurath MF, Becker C (2014). Immune-epithelial crosstalk at the intestinal surface. J Gastroenterol, 49:375-87.
22. Vimal J, Himal I, Kannan S (2020). Role of microbial dysbiosis in carcinogenesis & cancer therapies. Indian J Med Res, 152(6):553-61.
23. Sedighi M, Zahedi Bialvaei A, Hamblin MR, et al (2019). Therapeutic bacteria to combat cancer; current advances, challenges, and opportunities. Cancer Med, 8(6):3167-81.
24. Moosazadeh Moghaddam M, Bolouri S, Golmohammadi R, et al (2023). Targeted delivery of a short antimicrobial peptide (CM11) against Helicobacter pylori gastric infection using concanavalin A-coated chitosan nanoparticles. J Mater Sci Mater Med, 34(9):44.
25. Drago L (2019). Probiotics and colon cancer. Microorganisms, 7(3):66.
26. Li Y, Wu J, Qiu X, et al (2022). Bacterial outer membrane vesicles-based therapeutic platform eradicates triple-negative breast tumor by combinational photodynamic/chemo-/immunotherapy. Bioact Mater, 20:548-560.
27. Park K-S, Choi K-H, Kim Y-S, et al (2010). Outer membrane vesicles derived from Escherichia coli induce systemic inflammatory response syndrome. PLoS One, 5(6):e11334.
28. Kulkarni HM, Nagaraj R, Jagannadham MV (2015). Protective role of E. coli outer membrane vesicles against antibiotics. Microbiol Res, 181:1-7.
29. Imamiya R, Shinohara A, Yakura D, et al (2023). Escherichia coli-derived outer membrane vesicles relay inflammatory responses to macrophage-derived exosomes. mBio, 14(1):e0305122.
30. Jin L, Zhang Z, Tan X, et al (2022). Antitumor effect of Escherichia coli-derived outer membrane vesicles on neuroblastoma in vitro and in vivo: Effect of E. coli-OMVs on neuroblastoma. Acta Biochim Biophys Sin (Shanghai), 54(9):1301-1313.
31. Kim OY, Park HT, Dinh NTH, et al (2017). Bacterial outer membrane vesicles suppress tumor by interferon-γ-mediated antitumor response. Nat Commun, 8(1):626.
32. Alizadeh S, Esmaeili A, Omidi Y (2020). Anti-cancer properties of Escherichia coli Nissle 1917 against HT-29 colon cancer cells through regulation of Bax/Bcl-xL and AKT/PTEN signaling pathways. Iran J Basic Med Sci, 23(7):886-893.
33. Yang J, Hwang I, Lee E, et al (2020). Bacterial outer membrane vesicle-mediated cytosolic delivery of flagellin triggers host NLRC4 canonical inflammasome signaling. Front Immunol, 11:581165.
| Files | ||
| Issue | Vol 54 No 6 (2025) | |
| Section | Original Article(s) | |
| Keywords | ||
| E. coli CT-26 Colorectal cancer Apoptosis Inflammation | ||
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How to Cite
1.
Ghiyasvand M, hesampour A, Dabiri H, Arasteh J. Anticancer effects of Escherichia coli-derived outer membrane vesicles against colorectal cancer cells through regulation of apoptosis. Iran J Public Health. 2025;54(6):1310-1319.
