Anti-proliferative effects of physiological concentrations of enterolactone in models of prostate tumourigenesis

Authors

  • Mark J. McCann,

    Corresponding author
    • Food Nutrition & Health, Food and Bio-based Products, AgResearch Grasslands Research Centre, Palmerston North, New Zealand
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  • Ian R. Rowland,

    1. Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading, UK
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  • Nicole C. Roy

    1. Food Nutrition & Health, Food and Bio-based Products, AgResearch Grasslands Research Centre, Palmerston North, New Zealand
    2. The Riddet Institute, Massey University, Palmerston North, New Zealand
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Correspondence: Dr. Mark J. McCann, Food Nutrition & Health, Food and Bio-based Products, AgResearch Grasslands Research Centre, Private Bag 11008, Palmerston North 4442, New Zealand

E-mail: mark.mccann@agresearch.co.nz

Fax: +64-6-351-8003

Abstract

Scope

There is evidence that a mammalian lignan, enterolactone (ENL), decreases the proliferation rate of prostate cancer cells, although previous studies have used concentrations difficult to achieve through dietary modification. We have therefore investigated the anti-proliferative effects of ENL in an in vitro model of prostate tumourigenesis at concentrations reported to occur in a range of male populations.

Methods and results

The effects of 0.1 and 1 μM ENL on three markers of viability and proliferation (metabolic activity, growth kinetics, and cell cycle progression) were assessed in the RWPE-1, WPE1-NA22, WPE1-NB14, WPE1-NB11, WPE1-NB26, LNCaP, and PC-3 cell lines over 72 h. Based on these data, we quantified the expression levels of 12 genes involved in the control of DNA replication initiation using TaqMan real-time PCR in the WPE1-NA22, WPE1-NB14, WPE1-NB11, and WPE1-NB26 cell lines. ENL significantly inhibited the abnormal proliferation of the WPE1-NB14 and WPE1-NB11 cell lines and appears to be a consequence of decreased expression of abnormal chromatin licensing and DNA replication factor 1.

Conclusion

In contrast to previous studies, concentrations of ENL that are reported after dietary intervention restrict the proliferation of early-stage tumourigenic prostate cell lines by inhibiting the abnormal formation of complexes that initiate DNA replication.

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