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Cell-free supernatant of Clostridium butyricum induces mitochondrial apoptosis and suppresses NF-κB pathway in colorectal cancer cells.

Immunobiology 2026 Vol.231(2) p. 153172

Liu M, Liu S, Xie W, Li G, Deng T

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[BACKGROUND] Clostridium butyricum (CB), a butyrate-producing probiotic, exhibits antitumor potential in colorectal cancer (CRC).

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APA Liu M, Liu S, et al. (2026). Cell-free supernatant of Clostridium butyricum induces mitochondrial apoptosis and suppresses NF-κB pathway in colorectal cancer cells.. Immunobiology, 231(2), 153172. https://doi.org/10.1016/j.imbio.2026.153172
MLA Liu M, et al.. "Cell-free supernatant of Clostridium butyricum induces mitochondrial apoptosis and suppresses NF-κB pathway in colorectal cancer cells.." Immunobiology, vol. 231, no. 2, 2026, pp. 153172.
PMID 41830660

Abstract

[BACKGROUND] Clostridium butyricum (CB), a butyrate-producing probiotic, exhibits antitumor potential in colorectal cancer (CRC). This study investigated the direct effects and mechanisms of CB-secreted metabolites on CRC cells.

[METHODS] HT-29 cells were treated with serial dilutions (5-40%) of sterile-filtered CB supernatant (CBS), using E. coli DH5α supernatant as control. Cell viability and proliferation were assessed by CCK-8 and Ki-67 immunofluorescence. Apoptosis was evaluated by Annexin V/PI flow cytometry. Mitochondrial membrane potential (ΔΨm) was monitored via JC-1 staining. Apoptosis-related and NF-κB pathway proteins were analyzed by Western blot.

[RESULTS] The CBS notably suppressed HT-29 cell viability and proliferation as concentration and treatment duration increased, with an IC₅₀ of 18.84% (95% CI: 16.2% to 21.5%) at 48 h. CBS exposure markedly increased apoptotic cell proportion. Mechanistically, CBS induced ΔΨm loss, cytosolic cytochrome c translocation, and activation of caspase-9 and -3. Concurrently, CBS inhibited NF-κB pathway activation, downregulated Bcl-2, and upregulated Bax.

[CONCLUSION] CB culture supernatant inhibits growth and induces apoptosis in HT-29 cells through mitochondrial dysfunction and NF-κB suppression.

MeSH Terms

Humans; Clostridium butyricum; Apoptosis; NF-kappa B; Colorectal Neoplasms; Mitochondria; Signal Transduction; HT29 Cells; Membrane Potential, Mitochondrial; Cell Proliferation; Cell Survival; Probiotics; Culture Media, Conditioned; Caspase 9; Proto-Oncogene Proteins c-bcl-2; Cytochromes c

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