The anti-proliferative effects of enterolactone in prostate cancer cells: evidence for the role of DNA licencing genes, mi-R106b cluster expression, and PTEN dosage.
The mammalian lignan, enterolactone, has been shown to reduce the proliferation of the earlier stages of prostate cancer at physiological concentrations in vitro. However, efficacy in the later stages of the disease occurs at concentrations difficult to achieve through dietary modification. We have therefore investigated what concentration(s) of enterolactone can restrict proliferation in multiple stages of prostate cancer using an in vitro model system of prostate disease. We determined that enterolactone at 20 μM significantly restricted the proliferation of mid and late stage models of prostate disease. These effects were strongly associated with changes in the expression of the DNA licencing genes (GMNN, CDT1, MCM2 and 7), in reduced expression of the miR-106b cluster (miR-106b, miR-93, and miR-25), and in increased expression of the PTEN tumour suppressor gene. We have shown anti-proliferative effects of enterolactone in earlier stages of prostate disease than previously reported and that these effects are mediated, in part, by microRNA-mediated regulation.
Food Nutrition & Health, Food and Bio-based Products, AgResearch Grasslands Research Centre, Palmerston North 4442, New Zealand. mark.mccann@agresearch.co.nz.
Mark J
MJ
McCann
Department of Food and Nutritional Sciences, P.O. Box 226, Whiteknights, Reading RG6 6AP, UK. i.rowland@reading.ac.uk.
Ian R
IR
Rowland
Food Nutrition & Health, Food and Bio-based Products, AgResearch Grasslands Research Centre, Palmerston North 4442, New Zealand. nicole.roy@agresearch.co.nz.
Nicole C
NC
Roy
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D017705:Lignans; C542541:MIRN106 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D015107:4-Butyrolactone; C029497:2,3-bis(3'-hydroxybenzyl)butyrolactone