RRC ID 78747
Author Tomii A, Higa M, Naito K, Kurata K, Kobayashi J, Takei C, Yuasa K, Koto Y, Shimizu H.
Title Activation of the TLR4-JNK but not the TLR4-ERK pathway induced by indole-3-acetic acid exerts anti-proliferative effects on Caco-2 cells.
Journal Biosci Biotechnol Biochem
Abstract We previously found that indole-3-acetic acid (IAA) produced from tryptophan by gut microbiota decreases the expression of tumor necrosis factor α (TNFα), which is implicated in the pathogenesis of colorectal cancer (CRC). The present study aimed to determine IAA involvement in the proliferation of CRC-derived Caco-2 cells. Cell proliferation was suppressed by IAA, whereas IAA-induced aryl hydrocarbon receptor activation had no impact. IAA activated extracellular signal-related (ERK) and c-Jun N-terminal (JNK) kinases, but not p38. Toll-like receptor 4 (TLR4) may be required to activate ERK and JNK, but only the TLR4-JNK pathway might elicit the anti-proliferative effects of IAA. Thus, IAA may be a ligand for TLR4 that contributes to inhibiting CRC cell proliferation by activating TLR4-mediated JNK. Because IAA did not induce cytotoxicity, inhibiting cell cycle progression might affect the anti-proliferative capacity of IAA. Therefore, colonic IAA accumulation might help to prevent CRC development and progression.
Volume 87(8)
Pages 839-849
Published 2023-7-24
DOI 10.1093/bbb/zbad055
PII 7153323
PMID 37147026
MeSH Caco-2 Cells Humans JNK Mitogen-Activated Protein Kinases / metabolism MAP Kinase Signaling System* Toll-Like Receptor 4* / metabolism p38 Mitogen-Activated Protein Kinases / metabolism
Human and Animal Cells CACO-2(RCB0988)