Gut microbiota derived butyrate suppresses colorectal cancer via phosphoinositide three kinase and protein kinase B signaling

Abstract

BACKGROUND

Colorectal cancer (CRC) remains a major cause of cancer-related morbidity and mortality. Faecalibacterium prausnitzii (FP) is a major butyrate-producing intestinal bacterium, and sodium butyrate (NaB) has recognized epigenetic and antitumor effects. However, whether FP extract and NaB exert comparable effects on CRC cells and whether these effects are associated with histone deacetylase activity and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling remain unclear. We hypothesized that both treatments suppress CRC growth and promote apoptosis through histone deacetylase-associated molecular changes.

AIM

To determine the antitumor effects of FP extract and NaB and their associated molecular changes.

METHODS

Six CRC cell lines and two normal colorectal cell lines were treated with FP extract or NaB. Cell viability, apoptosis, and apoptosis-related and PI3K/AKT proteins were assessed. SW480 cells were used for detailed analyses with inhibitor of trichostatin A-1. Eighteen nude mice were allocated to control, FP, or FP plus inhibitor groups. Student’s t test or one-way analysis of variance was used.

RESULTS

Both treatments reduced viability and increased apoptosis in all six CRC cell lines, without significant effects in normal colorectal cells. In SW480 cells, apoptosis was 5.28% ± 0.78% in controls, 37.94% ± 2.49% after FP extract, and 47.15% ± 0.94% after NaB treatment (P < 0.05). Both treatments increased cleaved caspase-3 and B-cell lymphoma 2-associated X protein and decreased B-cell lymphoma 2, PI3K, and phosphorylated AKT (P < 0.05); inhibitor of trichostatin A-1 partially reversed these changes. In mice, FP reduced final tumor volume (2.37 ± 0.15 mm³ vs 0.43 ± 0.05 mm³) and weight (1.13 ± 0.13 g vs 0.25 ± 0.04 g; P < 0.05), whereas inhibitor treatment attenuated these effects.

CONCLUSION

FP extract and NaB suppress CRC cells, while FP reduces tumor growth in mice through associated epigenetic and signaling changes.

Keywords: Colorectal cancer; Faecalibacterium prausnitzii; Sodium butyrate; Apoptosis; Histone deacetylase activity; Phosphoinositide 3-kinase/protein kinase B signaling

Core Tip: Faecalibacterium prausnitzii extract and sodium butyrate selectively inhibited proliferation and promoted apoptosis in six colorectal cancer cell lines without significantly affecting normal colorectal cells. Faecalibacterium prausnitzii also reduced tumor growth in mice. Inhibitor of trichostatin A-1 partially reversed these effects, linking the observed responses to histone deacetylase activity and phosphoinositide 3-kinase/protein kinase B-related signaling changes. However, the findings remain associative and do not establish a direct causal pathway.