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Suppression of tumour development by substances derived from the diet--mechanisms and clinical implications
A Gescher1, U Pastorino, S M Plummer
1MRC Toxicology Unit, University of Leicester, London.
Abstract:
The concept that cancer can be prevented, or its onset postponed, by certain diet-derived substances is currently eliciting considerable interest. Agents which interfere with tumour development at the stage of promotion and progression in particular are of potential clinical value. As chemopreventive agents have to be administered over a long period of time in order to establish whether they possess efficacy in humans, it is of paramount importance to establish their lack of toxicity. The desire to select the best chemopreventive drug candidates for clinical trial, and the necessity to monitor efficacy in the short and intermediate term, render the identification of specific mechanism-based in vivo markers of biological activity a high priority. Antioxidation, inhibition of arachidonic acid metabolism, modulation of cellular signal transduction pathways, inhibition of hormone and growth factor activity and inhibition of oncogene activity are discussed as mechanisms by which the soya constituent genistein, the curry ingredient curcumin and the vitamin A analogue 13-cis retinoic acid exert tumour suppression. A better understanding of these mechanisms will help the establishment of screens for the discovery of new and better chemopreventive agents and the identification of surrogate markers to assess the outcome of clinical chemoprevention trials.
Insights
Dietary compounds like genistein and curcumin show promise for cancer prevention by targeting tumor promotion and progression. Identifying their mechanisms and biomarkers is crucial for developing effective, safe chemopreventive agents.
Area of Science:
- Oncology
- Nutritional Science
- Pharmacology
Background:
- Dietary substances are increasingly recognized for their potential in cancer prevention.
- Chemopreventive agents require long-term administration, necessitating toxicity assessment and efficacy monitoring.
- Identifying mechanism-based biomarkers is critical for selecting drug candidates and evaluating clinical trials.
Purpose of the Study:
- To explore the potential of diet-derived substances as chemopreventive agents.
- To highlight the importance of understanding the mechanisms of action for tumor suppression.
- To emphasize the need for in vivo markers to assess biological activity and efficacy.
Main Methods:
- Review of proposed mechanisms of chemoprevention by specific dietary compounds.
- Discussion of antioxidation, metabolic inhibition, and signaling pathway modulation.
- Examination of genistein, curcumin, and 13-cis retinoic acid as examples.
Main Results:
- Genistein, curcumin, and 13-cis retinoic acid demonstrate tumor suppression through various mechanisms.
- These mechanisms include antioxidation, inhibition of arachidonic acid metabolism, and modulation of cellular pathways.
- Understanding these mechanisms aids in discovering new chemopreventive agents and surrogate markers.
Conclusions:
- Dietary compounds offer promising avenues for cancer chemoprevention.
- Further research into their mechanisms and the development of reliable biomarkers are essential for clinical application.
- This knowledge will facilitate the discovery of novel agents and improve the assessment of clinical trial outcomes.