• Cruciferous vegetables and colo-rectal cancer.

      Lynn, Anthony; Collins, Andrew; Fuller, Zoë; Hillman, Kevin; Ratcliffe, Brian (2006-02)
      Cruciferous vegetables have been studied extensively for their chemoprotective effects. Although they contain many bioactive compounds, the anti-carcinogenic actions of cruciferous vegetables are commonly attributed to their content of glucosinolates. Glucosinolates are relatively biologically inert but can be hydrolysed to a range of bioactive compounds such as isothiocyanates (ITC) and indoles by the plant-based enzyme myrosinase, or less efficiently by the colonic microflora. A number of mechanisms whereby ITC and indoles may protect against colo-rectal cancer have been identified. In experimental animals cruciferous vegetables have been shown to inhibit chemically-induced colon cancer. However, the results of recent epidemiological cohort studies have been inconsistent and this disparity may reflect a lack of sensitivity of such studies. Possible explanations for the failure of epidemiological studies to detect an effect include: assessment of cruciferous vegetable intake by methods that are subject to large measurement errors; the interaction between diet and genotype has not been considered: the effect that post-harvest treatments may have on biological effects of cruciferous vegetables has not been taken into account.
    • Vegetable-derived isothiocyanates: anti-proliferative activity and mechanism of action.

      Zhang, Yuesheng; Yao, Song; Li, Jun (2006-02)
      Many isothiocyanates (ITC), which are available to human subjects mainly through consumption of cruciferous vegetables, demonstrate strong cancer-preventive activity in animal models. Human studies also show an inverse association between consumption of ITC and risk of cancer in several organs. Whereas earlier studies primarily focused on the ability of ITC to inhibit carcinogen-activating enzymes and induce carcinogen-detoxifying enzymes, more recent investigations have shown that ITC inhibit the proliferation of tumour cells both in vitro and in vivo by inducing apoptosis and arresting cell cycle progression. ITC cause acute cellular stress, which may be the initiating event for these effects. These findings shed new light on the mechanism of action of ITC and indicate that ITC may be useful both as cancer-preventive and therapeutic agents. ITC activate caspase 9-mediated apoptosis, apparently resulting from mitochondrial damage, and also activate caspase 8, but the mechanism remains to be defined. Cell cycle arrest caused by ITC occurs mainly in the G2/M phase, and both the G2 and M phases are targetted; critical G2-phase regulators, including cyclin B1, cell division cycle (Cdc) 2 and Cdc25C, are down regulated or inhibited, and tubulin polymerization and spindle assembly are disrupted. Moreover, ITC are metabolized in vivo through the mercapturic acid pathway, giving rise to thiol conjugates (dithiocarbamates). Studies show that these dithiocarbamates are similar to their parent ITC in exerting anti-proliferative activity. Taken together, dietary ITC are highly-promising anti-cancer agents, capable of targetting multiple cellular components that are important for tumour cell survival and proliferation.