S‐Allylcysteine Potently Protects against PhIP‐Induced DNA Damage via Nrf2/AhR Signaling Pathway Modulation in Normal Human Colonic Mucosal Epithelial Cells

Abstract

Scope 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. Methods and results 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. Conclusion 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.

Regulation of Xenobiotic-Metabolizing Enzymes by 5-Demethylnobiletin and Nobiletin to Mitigate Benzo[a]pyrene-Induced DNA Damage In Vitro and In Vivo

“…Several phytochemicals have shown inhibitory activity toward various CYP isoforms, indicating their potential as therapeutic agents for anticancer and chemoprevention. − Our results showed that B­[a]P increased the CYP family activity in NCM460 cells and liver tissue. However, giving 5-DMNB together with B­[a]P significantly decreased CYP activity in vitro and in vivo .…”