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

AbstractSCOPE:
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.
AuthorsMark J McCann, Ian R Rowland, Nicole C Roy
JournalMolecular nutrition & food research (Mol Nutr Food Res) Vol. 57 Issue 2 Pg. 212-24 (Feb 2013) ISSN: 1613-4133 [Electronic] Germany
PMID23148045 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Chemical References
  • Lignans
  • 4-Butyrolactone
  • 2,3-bis(3'-hydroxybenzyl)butyrolactone
Topics
  • 4-Butyrolactone (analogs & derivatives, pharmacology)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Cell Survival (drug effects)
  • Cell Transformation, Neoplastic (pathology)
  • DNA Replication (drug effects)
  • Humans
  • Lignans (pharmacology)
  • Male
  • Mitochondria (drug effects)
  • Prostatic Neoplasms (drug therapy, pathology)
  • Real-Time Polymerase Chain Reaction

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