s-allylcysteine and 2-amino-1-methyl-6-phenylimidazo(4-5-b)pyridine

This study aims to investigate whether S-allylcysteine (SAC) exerts chemoprophylactic effects on foodborne carcinogenicity caused by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in normal human colonic mucosal epithelial cells.. Cellular thermal shift assays show that SAC has an affinity for the Kelch-like ECH-associated protein 1 (Keap1) protein. Moreover, SAC may also dampen the binding of Keap1 and NF-E2-related factor 2 (Nrf2) by inhibiting p-p38 and increasing the phosphorylation of extracellular signal regulated kinases 1/2 (ERK1/2) and protein kinase B (AKT), thereby inducing Nrf2/heme oxygenase-1 (HO-1) signaling and upregulating the ratio of glutathione (GSH) to GSH/GSSG (oxidized glutathione), which inhibits PhIP-induced oxidative stress and DNA damage. In addition, SAC significantly downregulates the aryl hydrocarbon receptor signaling pathway, suggesting that SAC may potentially impede the metabolic transformation of carcinogens.. Collectively, these findings suggest that SAC protects against PhIP-induced reactive oxygen species production and DNA damage by modulating the Nrf2/AhR signaling pathway, which may have significant potential as a novel chemopreventive agent.

Topics: Cysteine; DNA Damage; Epithelial Cells; Glutathione; Heme Oxygenase-1; Humans; Imidazoles; Kelch-Like ECH-Associated Protein 1; NF-E2-Related Factor 2; Oxidative Stress; Signal Transduction