How it Works
Sulforaphane & Chemoprevention An estimated 1.4 million Americans will be diagnosed with cancer in 2005, with over 570,000 mortalities (American Cancer Society). Although advances in treatment have been made, there continues to be a need for intervention strategies, including compounds that act as primary protective agents by preventing, delaying, or reversing pre-neoplastic lesions, as well as those that act on secondary or recurrent cancers as therapeutic agents. Compounds found in the diet are of particular interest because of their accessibility to the general population, and ongoing research continues to identify novel candidates for use in cancer chemoprevention clinical trials. Isothiocyanates (ITCs) are found in cruciferous vegetables such as broccoli, Brussels sprouts, cauliflower, and cabbage. Sulforaphane (SFN) is an ITC found at high levels in broccoli and broccoli sprouts [1,2]. Since it was first identified in 1992 as a potential chemopreventive agent there has been a sharp increase in citations mentioning Sulforaphane. Early research focused on Phase 2 enzyme induction by Sulforaphane, as well as inhibition of enzymes involved in carcinogen activation, but there has been growing interest in other mechanisms of Chemoprotection by Sulforaphane. Thus, in addition to its ability to act as a ‘blocking’ agent against early initiating events, recent evidence points to SFN as a ‘suppressing’ agent, helping to delay or reverse growth and/or survival of transformed cells. The precise mechanism(s) that operate during the post initiation phase are not well understood, and only a handful of suppressing agents have been studied in any detail. Nonetheless, this review considers the evidence that Sulforaphane might represent a multi-faceted chemopreventive agent, with the ability to act during blocking, suppressing and therapeutic stages. The various mechanisms will be discussed in turn, namely: TOTAL BODY DETOXIFICATION (1) Inhibition of Phase 1 Enzymes: Phase I enzymes can metabolically activate pro carcinogens under certain conditions. IMPROVED IMMUNE SYSTEM RESPONSE (2) Modulation of Phase 2 Enzymes: Elevates Cellular Defenses leading to enhanced detoxification DESTROYS GASTROINTESTINAL PATHOGENS (3) Eradication of Infection: Although many studies with SFN have focused on detoxification of chemical carcinogens, evidence also has been reported for protective effects against viral or bacterial pathogens. For example, chronic infection with Helicobacter pylori (H. pylori) is associated with an increased risk of gastric cancer. REPAIRED DNA DAMAGE TO SKIN FROM UVB IRRADIATION (4) Inhibition of Growth Promoting Signaling Pathways: Sulforaphane inhibited UVB induced AP-1 activation in human keratinocytes at concentrations ranging from 1 to 10 Μm. It was shown that SFN interfered with AP-1binding to DNA, and cysteine residues in AP-1 may be important for the inhibitory effects. COLON AND PROSTATE HEALTH (5) Alteration of Signaling Pathways, Cell Cycle Arrest, and Apoptosis: The effects of SFN on cell viability were described in HT-29 human colon cancer cells, where 100 μM SFN for 24 or 48 h resulted in a decrease in cell viability to 10% of controls…… Furthermore, there was an increase in Bax protein expression, loss of cytochrome c from mitochondria, and concomitant elevation of cytosolic cytochrome c…… Similar responses have been observed in human prostate cancer cells after treatment with SFN. Androgen-dependent LnCaP cells exposed to 9 μM SFN underwent a G1 arrest, whereas increasing the dose to 50 μM caused the cells to become apoptotic, CHEMOPROTECTION (6) Inhibition of Recurrence: Accumulating evidence suggests that SFN is a highly promising dietary preventive agent, due to its ability to confer Chemoprotection through several distinct pathways and via multiple mechanisms of action. This information was reprinted from: NIH Public Access
Author Manuscript Cancer Lett. Author manuscript; available in PMC 2008 March 29.
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