Systematic Review of the Inhibitory Effects of Naturally Occurring Isothiocyanates on Human Cytochrome P450 1A1: Implications for Dietary Chemoprevention

Abstract

Background: Isothiocyanates (ITCs), particularly sulforaphane, have been implicated in the modulation of cytochrome P450 enzymes, such as CYP1A1, which play a crucial role in the metabolism of various xenobiotics and carcinogens. This review synthesizes the findings from multiple studies regarding the impact of ITCs on CYP1A1 expression and activity in different experimental settings.

Objective: To examine the effects of different ITCs, including sulforaphane and phenethyl isothiocyanate, on CYP1A1 activity and gene expression across various study designs, populations, and doses.

Methods: A comprehensive review of in vitro and in vivo studies, along with in silico analyses, that investigated the relationship between ITCs and CYP1A1. Studies were selected based on their relevance to CYP1A1 modulation and its potential health implications.

Results: Several studies demonstrated that ITCs, including sulforaphane, significantly modulate CYP1A1 activity, either by inhibiting its expression or altering its enzymatic function. While some studies focused on the direct inhibition of CYP1A1 in cancer cells, others highlighted age-related changes in CYP1A1 mRNA levels in animal models. Additionally, in silico studies explored the molecular mechanisms through which sulforaphane impacts CYP1A1 activity in neurological disorders, such as Alzheimer's disease.

Conclusion: ITCs, particularly sulforaphane, have demonstrated potential for modulating CYP1A1 activity in various biological contexts. This modulation may play a critical role in the chemopreventive properties of these compounds, warranting further research into their therapeutic implications for cancer prevention and other health benefits.