Dietary Chemopreventive Phytochemicals: Too Little or Too Much?

Abstract

There is a large body of evidence that the consumption of fruit and vegetables can decrease the risk of cancer. However, the link between diet and health is extremely complex. Some dietary phytochemicals seem to offer protection in an exposure-related manner and many molecular targets and signaling pathways affected by phytochemicals have been discovered. Although in vitro studies have contributed significantly to our understanding, quite a number use concentrations orders of magnitude greater than those achievable in humans or toxic to normal tissues (exemplified by toxic concentrations of indole-3-carbinol, epigallocatechin-3-gallate, curcumin, and genistein for breast cells). Such studies may produce results that are physiologically irrelevant, thus hindering predictions of efficacy. Here, we argue for careful consideration to be given to the in vitro experimental conditions under which dietary phytochemicals are investigated. Design features, such as the use of appropriate nontoxic concentrations, extended treatment times, three-dimensional cultures, primary tumor cultures, and comparison of susceptibility of various cancer subtypes, should improve our understanding of their molecular targets. This in turn would facilitate predictions as to their potential usefulness in the clinic. Chemopreventive Effect of Vegetables and FruitDiet is thought to contribute to a significant proportion of cancer cases and about a third of mortalities (1). Several international committees previously concluded that consumption of fruit and vegetables decreases the risk of cancer (2-4). More recently, the second WCRF-AICR report (5) found that overall, the evidence that vegetables and fruit protect against cancer is less impressive. However, among specific groups, Allium vegetables and garlic were considered to offer probable protection against stomach and colorectal cancers, respectively. Other groups, e.g., cruciferous vegetables [source of isothiocyanates (ITC) and indoles] or tea (source of polyphenols), received little attention in this report. The International Agency for Research on Cancer concluded that consumption of cruciferous vegetables is associated with a modest risk reduction for cancers at some sites, although the reductions are no greater than those observed with total vegetable uptake (6).Because of insufficient evidence, the conclusions of the latest WCRF-AICR report have somewhat undermined the hypothesis that specific phytochemicals, present in vegetables and fruit, may be responsible for chemoprevention. This lack of convincing evidence is partly because important contributing factors were not considered in many of the original studies. Many based on self-reporting are found to be biased. Factors, such as tobacco, gene polymorphisms, and body composition, can modify cancer risk (5). Significant differences in levels of consumed vegetables, and consequently dietary phytochemicals, are found among various populations. For example, the highest levels of cruciferous vegetable uptake in Europe and North A...

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