Glucosinolates: paradoxically beneficial in fighting both brain cell death and cancer

Abstract Glucoraphanin is a glucosinolate prominently found in the cruciferous vegetables, broccoli, and broccoli sprouts. Following plant tissue damage, glucoraphanin combines with the enzyme myrosinase to form the isothiocyanate, sulforaphane. Sulforaphane is a natural health product with properties that have paradoxical effects. On the one hand it has been shown to be profoundly protective of cell death as a neuroprotective agent for neurodegenerative diseases, and on the other hand, it has been shown to be proapoptotic as an anticancer agent. Our laboratory has found broccoli sprouts and sulforaphane to be “protective” of the fetal brain in preclinical rodent models of placental insufficiency, fetal inflammation, and perinatal stroke. However, research intended to provide preventive strategies to the fetus, via the pregnant mother is sparse and difficult to undertake. This is especially true of conventional pharmaceuticals, likely related to the fear of litigation. This review sought to investigate the different mechanisms of action of sulforaphane when used as an antiapoptotic agent, versus as a proapoptotic agent in a cancer setting. Literature in maternal health and sulforaphane showed a pattern of low doses of sulforaphane acting as a phase II enzyme inducer and promotes antioxidant enzymes to reduce oxidative stress, thereby preventing cell death. Reviewing literature of sulforaphane as an anticancer agent, including our own studies in cell culture, shows that higher doses of sulforaphane act as a proapoptotic agents and possible HDAC inhibitors, leading to the death of a host of different types of cancer cells.