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Dietary chemopreventive phytochemicals: too little or too much?
Elena P Moiseeva1, Margaret M Manson
1Cancer Biomarkers and Prevention Group, Department of Cancer Studies and Molecular Medicine, University of Leicester, University Road, Leicester LE1 7RH, United Kingdom. em9@le.ac.uk
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.
Insights
Dietary phytochemicals show promise in cancer prevention, but in vitro studies often use unrealistic concentrations. Optimizing experimental conditions is crucial for accurate efficacy predictions in cancer research.
Area of Science:
- Nutritional biochemistry
- Cancer biology
- In vitro study design
Background:
- Fruit and vegetable consumption is linked to reduced cancer risk.
- Dietary phytochemicals have demonstrated cancer-protective effects through various molecular targets.
- In vitro studies are vital but often employ non-physiologically relevant concentrations of phytochemicals.
Purpose of the Study:
- To highlight the limitations of current in vitro studies on dietary phytochemicals.
- To advocate for improved experimental designs in phytochemical research.
- To enhance the clinical relevance of in vitro findings.
Main Methods:
- Critique of existing in vitro study methodologies for phytochemicals.
- Proposal of optimized experimental conditions for in vitro research.
- Emphasis on using non-toxic concentrations and extended treatment times.
Main Results:
- Many in vitro studies utilize concentrations of phytochemicals that are toxic or unachievable in humans.
- Physiologically irrelevant results from in vitro studies hinder accurate efficacy predictions.
- Improved experimental designs can lead to more reliable data.
Conclusions:
- Careful consideration of in vitro experimental conditions is essential for studying dietary phytochemicals.
- Implementing appropriate concentrations, longer treatment durations, and advanced culture models will improve understanding.
- Optimized in vitro studies will facilitate the prediction of phytochemicals' clinical utility in cancer treatment.
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