Induction of quinone reductase by sulforaphane and sulforaphane N-acetylcysteine conjugate in murine hepatoma cells

Abstract

Broccoli belongs to a group of vegetables termed cruciferous vegetables and characterized by their glucosinolate content. These glucosinolates are secondary metabolites that, upon hydrolysis, release bioactive isothiocyanates (ITCs). Bioactive ITCs are considered to protect the body from cancer by inducing detoxification enzymes such as quinone reductase (QR). This has the potential to make dietary choice a powerful strategy for achieving protection against carcinogenesis, mutagenesis, and other forms of toxicity from xenobiotic electrophiles and reactive forms of oxygen. The bioactive ITC sulforaphane (SF) is the hydrolysis product of glucoraphanin, the predominant aliphatic glucosinolate in broccoli. Because SF appears more potent than many other ITCs in induction of detoxification enzymes, it may have potential as a dietary cancer-preventative agent. One potential concern is that SF is highly reactive and has a very short half-life in the body, forming a glutathione conjugate that is further metabolized to the N-acetyl-L-cysteine conjugate (SF-NAC), the major excretory product found in the urine. However, the conjugate is a reversible complex, able to release free SF. The objective of this study was to compare QR-inducing activity by SF and its major metabolite SF-NAC, in murine hepatoma cells. Both SF and SF-NAC caused dose-related cell growth inhibition and QR induction. SF, 1 and 2 microM, resulted in a 3.0- and 3.5-fold induction of QR, respectively, and the same concentrations of SF-NAC caused a similar, although somewhat greater, induction of QR, 3.8- and 4.5-fold, respectively. These results strengthen the basis for considering that an effective therapeutic form of SF may be the ITC conjugate, formed in situ or given in place of purified ITC as prophylactic treatment to individuals at high risk for cancer.