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There is growing interest in the ability of phytochemicals to prevent chronicdiseases,such as cancer and heart disease.However,some of these agents havepoor bioavailability and many of the in-depth studies into their mechanisms ofaction have been carried out in vitro using doses which are unachievable inhumans.In order to optimize the design of chemopreventive treatment,it is impor-tant to determine which of the many reported mechanisms of action are clinicallyrelevant.In this review we consider the physiologically achievable doses for afew of the best studied agents (indole-3-carbinol,diindolylmethane,curcumin,epigallocatechin-3-gallate and resveratrol) and summarize the data derived fromstudies using these low concentrations in cell culture.We then cite examples of invitro effects which have been observed in vivo.Finally,the ability of agentcombinations to act synergistically or antagonistically is considered.We con-clude that each of the compounds shows an encouraging range of activities invitro at concentrations which are likely to be physiologically relevant.There arealso many examples of in vivo studies which validate in vitro observations.Animportant consideration is that combinations of agents can result in significantactivity at concentrations where any single agent is inactive.Thus,for each of thecompounds reviewed here,in vitro studies have provided useful insights intotheir mechanisms of action in humans.However,data are lacking on the full rangeof activities at low doses in vitro and the benefits or otherwise of combinations invivo.
There is growing interest in the ability of phytochemicals to prevent chronic diseases, such as cancer and heart disease. Despite some of these agents have poor bioavailability and many of the in-depth studies into their mechanisms ofaction have been carried out in vitro using doses which are unachievable inhumans.In order to optimize the design of chemopreventive treatment, it is impor-tant to determine which of the many reported mechanisms of action are clinicallyrelevant.In this review we consider the physiologically achievable doses for afew of the best studying agents (indole- 3-carbinol, diindolylmethane, curcumin, epigallocatechin-3-gallate and resveratrol) and summarize the data derived from materials using these low concentrations in cell culture. We then cite examples of invitro effects which have been observed in vivo. Infinally, the ability of agentcombinations to act synergistically or antagonistically is considered.We con-clude that each of the compounds shows an encouraging range of activ ities invitro at concentrations which are likely to be physiologically relevant. Here are many many examples of in vivo studies which validate in vitro observations. A nimportant consideration is that combinations of agents can result in significantactivity at concentrations where any single agent is inactive. of the compound reviewed here, in vitro studies have provided useful insights intothe mechanisms of action in humans. However, data are lacking on the full range of activities at low doses in vitro and the benefits or otherwise of combinations invivo.