alexa Dietary flavonoids: effects on xenobiotic and carcinogen metabolism.
Bioinformatics & Systems Biology

Bioinformatics & Systems Biology

Journal of Computer Science & Systems Biology

Author(s): Moon YJ, Wang X, Morris ME

Abstract Share this page

Abstract Flavonoids are present in fruits, vegetables and beverages derived from plants (tea, red wine), and in many dietary supplements or herbal remedies including Ginkgo Biloba, Soy Isoflavones, and Milk Thistle. Flavonoids have been described as health-promoting, disease-preventing dietary supplements, and have activity as cancer preventive agents. Additionally, they are extremely safe and associated with low toxicity, making them excellent candidates for chemopreventive agents. The cancer protective effects of flavonoids have been attributed to a wide variety of mechanisms, including modulating enzyme activities resulting in the decreased carcinogenicity of xenobiotics. This review focuses on the flavonoid effects on cytochrome P450 (CYP) enzymes involved in the activation of procarcinogens and phase II enzymes, largely responsible for the detoxification of carcinogens. A number of naturally occurring flavonoids have been shown to modulate the CYP450 system, including the induction of specific CYP isozymes, and the activation or inhibition of these enzymes. Some flavonoids alter CYPs through binding to the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, acting as either AhR agonists or antagonists. Inhibition of CYP enzymes, including CYP 1A1, 1A2, 2E1 and 3A4 by competitive or mechanism-based mechanisms also occurs. Flavones (chrysin, baicalein, and galangin), flavanones (naringenin) and isoflavones (genistein, biochanin A) inhibit the activity of aromatase (CYP19), thus decreasing estrogen biosynthesis and producing antiestrogenic effects, important in breast and prostate cancers. Activation of phase II detoxifying enzymes, such as UDP-glucuronyl transferase, glutathione S-transferase, and quinone reductase by flavonoids results in the detoxification of carcinogens and represents one mechanism of their anticarcinogenic effects. A number of flavonoids including fisetin, galangin, quercetin, kaempferol, and genistein represent potent non-competitive inhibitors of sulfotransferase 1A1 (or P-PST); this may represent an important mechanism for the chemoprevention of sulfation-induced carcinogenesis. Importantly, the effects of flavonoids on enzymes are generally dependent on the concentrations of flavonoids present, and the different flavonoids ingested. Due to the low oral bioavailability of many flavonoids, the concentrations achieved in vivo following dietary administration tend to be low, and may not reflect the concentrations tested under in vitro conditions; however, this may not be true following the ingestion of herbal preparations when much higher plasma concentrations may be obtained. Effects will also vary with the tissue distribution of enzymes, and with the species used in testing since differences between species in enzyme activities also can be substantial. Additionally, in humans, marked interindividual variability in drug-metabolizing enzymes occurs as a result of genetic and environmental factors. This variability in xenobiotic metabolizing enzymes and the effect of flavonoid ingestion on enzyme expression and activity can contribute to the varying susceptibility different individuals have to diseases such as cancer. As well, flavonoids may also interact with chemotherapeutic drugs used in cancer treatment through the induction or inhibition of their metabolism. This article was published in Toxicol In Vitro and referenced in Journal of Computer Science & Systems Biology

Relevant Expert PPTs

Relevant Speaker PPTs

  • Muhamed Fakhri Omer
    Cathodoluminescence petrography for provenance studies of the sandstones of Ora Formation (Devonian-Carboniferous), Iraqi Kurdistan Region, Northern Iraq
    PPT Version | PDF Version
  • Mustafa M Hariri
    Importance of methods’ selection in the geosciences studies and exploration
    PPT Version | PDF Version
  • Afsar Rahbar
    Studies of the importance of Cytomegalovirus infection in breast cancer
    PPT Version | PDF Version
  • Jim Polarine
    Case studies of human fl ora and spore contamination in clean rooms
    PPT Version | PDF Version
  • Gulay Yelken Demirel
    Challenges in parenteral formulation development studies and an evaluation from QbD point of view
    PPT Version | PDF Version
  • Jianfeng Hong
    Extractable and leachable studies of parenteral infusion and transfusion products
    PPT Version | PDF Version
  • Yosef Yarden
    Classically, the 3’untranslated region (3’UTR) is that region in eukaryotic protein-coding genes from the translation termination codon to the polyA signal. It is transcribed as an integral part of the mRNA encoded by the gene. However, there exists another kind of RNA, which consists of the 3’UTR alone, without all other elements in mRNA such as 5’UTR and coding region. The importance of independent 3’UTR RNA (referred as I3’UTR) was prompted by results of artificially introducing such RNA species into malignant mammalian cells. Since 1991, we found that the middle part of the 3’UTR of the human nuclear factor for interleukin-6 (NF-IL6) or C/EBP gene exerted tumor suppression effect in vivo. Our subsequent studies showed that transfection of C/EBP 3’UTR led to down-regulation of several genes favorable for malignancy and to up-regulation of some genes favorable for phenotypic reversion. Also, it was shown that the sequences near the termini of the C/EBP 3’UTR were important for its tumor suppression activity. Then, the C/EBP 3’UTR was found to directly inhibit the phosphorylation activity of protein kinase CPKC in SMMC-7721, a hepatocarcinoma cell line. Recently, an AU-rich region in the C/EBP 3’UTR was found also to be responsible for its tumor suppression. Recently we have also found evidence that the independent C/EBP 3’UTR RNA is actually exists in human tissues, such as fetal liver and heart, pregnant uterus, senescent fibroblasts etc. Through 1990’s to 2000’s, world scientists found several 3’UTR RNAs that functioned as artificial independent RNAs in cancer cells and resulted in tumor suppression. Interestingly, majority of genes for these RNAs have promoter-like structures in their 3’UTR regions, although the existence of their transcribed products as independent 3’UTR RNAs is still to be confirmed. Our studies indicate that the independent 3’UTR RNA is a novel non-coding RNA species whose function should be the regulation not of the expression of their original mRNA, but of some essential life activities of the cell as a whole.
    PPT Version | PDF Version
  • Arny L Blanchard
    Long-term environmental studies and stewardship in Alaska: A case study from Port Valdez
    PPT Version | PDF Version
  • Soha M Hamdy
    Biochemical studies on the effect of turmeric on breast cancer of rats
    PPT Version | PDF Version
  • Adel Nefzi
    “Adel Nefzi-Torrey-Pines-Institute-for-Molecular-Studies-USA-Diversity-Oriented-Synthesis-of-low-Molecular-Weight-Acyclic-and-Heterocyclic-Compounds-from-Resin-bound-Polyamides-Application-for-Drug-Discovery”
    PPT Version | PDF Version
  • Dalia Hussein Soliman
    “Dalia Hussein Soliman-Al-Azhar-University-Egypt-Design-synthesis-docking-and-QSAR-studies-of-novel-3-5-diaryl-pyrazole-derivatives-and-their-evaluation-as-antioxidants-and-as-Immunomodulators-inhibitors-of-TNF-α-IL-2-IL-6”
    PPT Version | PDF Version
  • Xiaomei Lu
    Ocean subsurface studies with the CALIPSO spaceborne lidar
    PPT Version | PDF Version
  • S Catherine Alexander
    Immunotoxicity of industrial effluents in fin fish: An alternative animal model for immunotoxicological studies
    PPT Version | PDF Version
  • Ferdinand N Mbagwu
    Ethnomedical studies of plants used for treatment of diseases in eastern part of Nigeria
    PPT Version | PDF Version
  • C Peter Waegemann
    How to implement Healthcare Enterprise Intelligence and Care Analytics
    PDF Version

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords