Inhibition of Neoplastic Transformation and Bioavailability of Dietary Flavonoid Agents

  • Adrian A. Franke
  • Robert V. Cooney
  • Laurie J. Custer
  • Lawrence J. Mordan
  • Yuichiro Tanaka
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 439)


Evaluation of unknown biological effects of chemicals including food plant products requires the assessment of bioactivity and bioavailability. Epidemiologic studies show consistently a cancer protective effect of fruit and vegetable consumption, but there is little understanding of which phytochemicals account for this observation. Commonly studied antioxidant micronutrients are less consistently correlated with cancer protection relative to the food groups themselves, suggesting that other phytochemicals or a combination of food products play key roles in preventing cancer. We investigated the effects of the predominant dietary flavonoids and isoflavonoids at inhibiting neoplastic transformation induced by 3methylcholanthrene in C3H 10T1/2 murine fibroblasts. We found that most phenolic agents tested were equal to or superior to known chemopreventive agents such as carotenoids or vitamins in effectiveness. Hesperetin, hesperidin and catechin were the most potent agents among the flavonoids tested, inhibiting transformation completely when applied at 1.0 μM after exposure to the carcinogen. Structure-activity comparison revealed that among the compounds tested, flavonoids with a vicinal diphenol structure in ring ‘B’ and a saturated ‘C’ ring exhibited the strongest effects. Most agents tested showed dose-dependent patterns. Interestingly, the soy isoflavonoids were weakly active except when applied in combination, suggesting a synergistic effect. In addition, HPLC techniques were developed for determining the bioavailability of isoflavonoids in human biological fluids including urine, plasma and breast milk. We observed a relatively fast absorption, distribution and elimination of isoflavonoids including a biphasic pattern probably due to enterohepatic circulation. Total peak isoflavone levels in urine, plasma and in breast milk were found to be 60 μM, 2 μM and 0.2 μM, respectively and were reached 8—12 hours after consumption of soy foods. Lev els detected in human body fluids were found to be highly active at inhibiting neoplastic transformation, especially considering synergistic effects observed for combinations of daidzein and genistein, the predominant isoflavonoids occurring in soy foods.


Breast Milk Neoplastic Transformation Human Body Fluid Dietary Flavonoid Transformation Assay 
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Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Adrian A. Franke
    • 1
  • Robert V. Cooney
    • 1
  • Laurie J. Custer
    • 1
  • Lawrence J. Mordan
    • 1
  • Yuichiro Tanaka
    • 1
  1. 1.Cancer Research Center of HawaiiHonoluluUSA

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