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Modulation of carcinogen-metabolizing cytochromes P450 by phytochemicals in humans
Wanda Baer-Dubowska1, Hanna Szaefer
1Poznan University of Medical Sciences, Department of Pharmaceutical Biochemistry, Poznań, Poland. baerw@ump.edu.pl
Introduction:
Cytochrome P450 (CYP) families 1 - 3, besides oxidizing environmental and dietary chemicals, leading to their elimination, catalyze the bioactivation of exogenous as well as endogenous carcinogens. Phytochemicals, particularly those which are active food components, were shown to be able to affect specific CYP expression and/or activity in animal models and in human in vitro systems. Human intervention studies involving healthy volunteers were also performed. This review describes human CYP modulation by naturally occurring phytochemicals which can not only affect carcinogen metabolism in humans, but also change the drug response.
Areas Covered:
The authors present an overview of carcinogens metabolizing human CYP modulation in different model systems as well as studies on human dietary intervention. Furthermore, the authors provide examples of the phytochemicals that affect CYP expression and activity.
Expert Opinion:
CYP, which are involved in carcinogen activation, can metabolize a range of substrates and inducing CYP by one substrate may also increase the metabolism of another. The ultimate proof of the efficacy of CYP modulation strategy for chemoprevention may be provided by clinical trials involving risk populations, which are difficult to perform. The new human-like models are highly desired for the study of modulation of carcinogen-metabolizing CYP.
Insights
Naturally occurring phytochemicals can modulate human Cytochrome P450 (CYP) enzymes, impacting carcinogen metabolism and drug response. This review explores how dietary compounds affect CYP activity, offering insights into chemoprevention strategies.
Area of Science:
- Biochemistry
- Pharmacology
- Toxicology
Background:
- Cytochrome P450 (CYP) enzymes (families 1-3) are crucial for metabolizing environmental and dietary compounds.
- CYPs also play a role in activating both exogenous and endogenous carcinogens.
- Phytochemicals, bioactive food components, can influence CYP expression and activity.
Purpose of the Study:
- To review the modulation of human CYP enzymes by naturally occurring phytochemicals.
- To discuss the impact of phytochemicals on carcinogen metabolism and drug response in humans.
- To highlight examples of phytochemicals affecting CYP activity.
Main Methods:
- Overview of studies on human CYP modulation by phytochemicals.
- Inclusion of data from animal models and in vitro human systems.
- Analysis of human intervention studies with healthy volunteers.
Main Results:
- Phytochemicals can alter specific CYP expression and/or activity.
- Modulation of CYPs affects the metabolism of carcinogens.
- Phytochemicals can also influence drug metabolism and response.
Conclusions:
- CYP induction by one substrate can alter the metabolism of other substrates.
- Clinical trials in risk populations are needed to confirm chemoprevention efficacy.
- Development of human-like models is essential for studying carcinogen-metabolizing CYP modulation.
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