Molecular Mechanisms of Anti-inflammation and Anti-cancer by 6-(Methylsulfinyl) hexyl Isothiocyanate

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Recently, a number of natural compounds with several chemoprevensive properties of anti-carcinogenesis, anti-tumorigenesis and anti-inflammation have been identified from our diet. Numerous epidemiological studies as well as experimental animal studies demonstrate that high intake of cruciferous vegetables such as broccoli, wasabi, cauliflower, and cabbage, protect against tumorigenesis.　Thus, cruciferous vegetables have been a focus of constant attention for potential use in 'cancer chemoprevention'.　6- (Methylsulfinyl) hexyl isothiocyanate (6-MITC) is a major allyl isothiocyanate occurring in wasabi (Wasabia japonica), which is a typical Japanese pungent spice.　Several studies have reported that 6-MITC has anti-cancer activity in vivo and in vitro, but the molecular mechanism is not completely elucidated.　Cyclooxygenase-2(COX-2) and inducible nitric oxide synthase(iNOS) are important enzymes that mediate inflammatory processes. Excess up-regulations of COX-2 and iNOS have been associated with several types of cancers as well as inflammatory disorders. We found that 6-MITC has strongly inhibitory effects of COX-2 and iNOS expression at the signaling level and at the transcription factor/promoter levels.　Moreover, molecular analysis demonstrated that 6-MITC blocked the expressions of COX-2 and iNOS by suppressing multiple signal transduction pathways to attenuate the activation of transcriptional factors. This review discusses the mechanisms underlying anti-cancer and anti-inflammation by 6-MITC with special focus on its effect on cellular signaling pathways regulating the expressions of COX-2 and iNOS.

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