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Cancer chemoprevention and apoptosis mechanisms induced by dietary polyphenolics
G Galati1, S Teng, M Y Moridani
1Department of Pharmacology, University of Toronto, Ontario, Canada.
Abstract:
This review summarises current knowledge on the various molecular chemopreventive or therapeutic mechanisms that may be involved when the administration of flavonoids or polyphenols prevented chemical carcinogenesis in animal models. These mechanisms can be subdivided into the following: 1) the molecular mechanisms involved in preventing carcinogen metabolic activation, 2) the molecular mechanisms for preventing tumour cell proliferation by inactivation or downregulation of prooxidant enzymes or signal transduction enzymes, 3) the molecular cell death mechanisms for the induction of tumour cell death (apoptosis) and the molecular mechanisms for the inhibition of isolated mitochondria functions. Many of the flavonoids and polyphenols found in diets, supplements or herbal medicine were also ranked using "accelerated cytotoxic mechanism screening" by a combinatorial approach utilising isolated rat hepatocytes. A strong correlation of an early collapse of the mitochondrial membrane potential and cell death was found for most of the cytotoxic polyphenols but did not occur with non-toxic polyphenols. This screening could prove useful for eliminating polyphenols that have the potential for adverse health effects and for selecting safe and effective polyphenolic candidates for further development as supplements for preventing cancer or cardiovascular disease. Safety concerns of flavonoid/polyphenol supplements are also reviewed.
Insights
Flavonoids and polyphenols show promise in preventing cancer through various molecular mechanisms. A new screening method identifies safe and effective polyphenols by assessing their impact on cell death and mitochondrial function.
Area of Science:
- Molecular Biology
- Pharmacology
- Toxicology
Background:
- Flavonoids and polyphenols are dietary compounds with potential chemopreventive properties.
- Their mechanisms against chemical carcinogenesis in animal models are complex and multifaceted.
- Understanding these mechanisms is crucial for developing effective cancer prevention strategies.
Purpose of the Study:
- To review the molecular mechanisms by which flavonoids and polyphenols prevent chemical carcinogenesis.
- To evaluate a novel screening method for assessing the safety and efficacy of polyphenols.
- To identify safe polyphenolic candidates for cancer and cardiovascular disease prevention.
Main Methods:
- Literature review of molecular mechanisms in chemoprevention.
- Utilized "accelerated cytotoxic mechanism screening" with isolated rat hepatocytes.
- Assessed mitochondrial membrane potential and cell death induction.
Main Results:
- Identified three main categories of molecular mechanisms: carcinogen metabolism, tumor cell proliferation inhibition, and induction of tumor cell death (apoptosis).
- A strong correlation was observed between early collapse of mitochondrial membrane potential and cytotoxicity for most polyphenols.
- Non-toxic polyphenols did not exhibit this mitochondrial effect, suggesting a safety indicator.
Conclusions:
- Flavonoids and polyphenols exert chemopreventive effects through diverse molecular pathways.
- Accelerated cytotoxic mechanism screening effectively identifies potentially harmful polyphenols based on mitochondrial dysfunction.
- This screening method aids in selecting safe and effective polyphenolic supplements for disease prevention.