Sulforaphane is a promising agent under preclinical evaluation in many models of disease prevention. This bioactive
phytochemical affects many molecular targets in cellular and animal models; however, amongst the most sensitive is Keap1, a key sensor for the adaptive stress response system regulated through the
transcription factor Nrf2. Keap1 is a sulfhydryl-rich
protein that represses Nrf2 signaling by facilitating the polyubiquitination of Nrf2, thereby enabling its subsequent proteasomal degradation. Interaction of
sulforaphane with Keap1 disrupts this function and allows for nuclear accumulation of Nrf2 and activation of its transcriptional program. Enhanced transcription of Nrf2 target genes provokes a strong cytoprotective response that enhances resistance to
carcinogenesis and other diseases mediated by exposures to electrophiles and
oxidants. Clinical evaluation of
sulforaphane has been largely conducted by utilizing preparations of broccoli or broccoli sprouts rich in either
sulforaphane or its precursor form in plants, a stable β-thioglucose conjugate termed
glucoraphanin. We have conducted a series of clinical trials in Qidong, China, a region where exposures to food- and air-borne
carcinogens has been considerable, to evaluate the suitability of broccoli sprout beverages, rich in either
glucoraphanin or
sulforaphane or both, for their bioavailability, tolerability, and pharmacodynamic action in population-based interventions. Results from these clinical trials indicate that interventions with well characterized preparations of broccoli sprouts may enhance the detoxication of
aflatoxins and air-borne toxins, which may in turn attenuate their associated health risks, including
cancer, in exposed individuals.