Sulforaphane: from chemoprevention to pancreatic cancer treatment?

Over the past several decades, research on the action of bioactive constituents of plants (ie, phytochemicals) has focused predominantly on their cancer-preventive properties. Evidence for a protective role for vegetables is strongest and most consistent for vegetables in the Cruciferae (Brassicaceae) plant family, such as broccoli, cabbage, Brussels sprouts and cauliflower.1^–4 Cruciferous vegetables are characterised by a unique phytochemistry: their high content of the sulfur-containing glucosinolates or β-thioglucoside N-hydroxysulfates with a side chain and sulfur-linked β-d-glucopyranose moiety.5 Hydrolysis of glucosinolates by a β-thioglucosidase (myrosinase), either in the plant or by gut bacteria, results in the formation of biologically active compounds such as isothiocyanates and indoles.6 These bioactive compounds are hypothesised to be responsible for the chemoprotective effects conferred by a high cruciferous vegetable intake.

Isothiocyanates may exert their protective effects through several distinct mechanisms. Of the isothiocyanates, sulforaphane, which is found in broccoli and broccoli sprouts at particularly high levels, has been the most extensively studied. Considerable attention has focused on sulforaphane as a “blocking” agent—that is, its ability to modulate the nuclear factor-erythroid-2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) pathway.7 Sulforaphane reacts with specific thiol groups on Keap1, promoting Nrf2 dissociation from Keap1, and allowing subsequent activation of antioxidant response element (ARE)-driven gene expression of phase II biotransformation enzymes (glutathione S-transferases, UDP-glucuronosyltransferases, etc.).7 However, sulforaphane acts by other mechanisms too. It induces cell cycle arrest and apoptosis in cancer cells, …