Signaling pathways and intracellular targets of sulforaphane mediating cell cycle arrest and apoptosis.
Abstract
Epidemiological studies have revealed an inverse correlation between the intake of cruciferous vegetables and the risk of certain types of cancer. In animal studies, results suggest that the anti-cancerous effect of cruciferous vegetables is due to isothiocyanates that exist as thioglucoside conjugates in a variety of edible plants, including broccoli cabbage for example. Among isothiocyanates (ITC), Sulforaphane (SF) has received a great deal of interest due to its potent anti-tumoral properties in carcinogen-treated animals. The molecular pathways mediating the effects of SF have not been fully elucidated. However, many studies have shown that SF (as well as other ITCs) can induce phase II drug metabolizing enzymes in vitro as well as in animals. This commonly occurs via the activation of a basic leucine zipper transcription factor, Nrf2. In addition, accumulating evidence now indicates that SF can inhibit the proliferation of cancer cells in culture through the induction of cell cycle arrest via the regulation of cell cycle protein levels and/or cyclin-dependent kinase activity, tubulin polymerization and histone acetylation. Furthermore, ITCs have been shown to induce apoptotic cell death via a P53 dependent or independent ...Continue Reading
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