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Growth Inhibitory, Antiandrogenic, and Pro-apoptotic Effects of Punicic Acid in LNCaP Human Prostate Cancer Cells.
MedLine Citation:
PMID:  21067181     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Prostate cancer is a commonly diagnosed cancer in men, and dietary chemoprevention by pomegranate (Punica granatum) extracts has shown noticeable benefits. In this study, we investigated the growth inhibitory, antiandrogenic, and pro-apoptotic effects of 13 pure compounds found in the pomegranate in androgen-dependent LNCaP human prostate cancer cells. Cells deprived of steroid hormones were exposed to increasing concentrations (1-100 μM) of pomegranate compounds in the presence of 0.1 nM dihydrotestosterone (DHT), and the inhibition of cell growth was measured by WST-1 colorimetric assay after a 4 day exposure. Four compounds, epigallocatechin gallate (EGCG), delphinidin chloride, kaempferol, and punicic acid, were found to inhibit DHT-stimulated cell growth at concentrations of 10 μM and above. These four pomegranate compounds inhibited DHT-stimulated androgen receptor nuclear accumulation and the expression of the androgen receptor-dependent genes prostate specific antigen and steroid 5α-reductase type 1 at concentrations ≥10 μM. We determined the possible contribution of apoptosis to the observed decrease in cell growth and found that three compounds, EGCG, kaempferol, and, in particular, punicic acid, induced DNA fragmentation after a 24 h treatment, at concentrations in the 10-100 μM range. Punicic acid, an important fatty acid in pomegranate seeds, was further found to induce intrinsic apoptosis via a caspase-dependent pathway. In conclusion, punicic acid, the main constituent of pomegranate seed (70-80%), exhibited potent growth inhibitory activities in androgen-dependent LNCaP cells, which appear to be mediated by both antiandrogenic and pro-apoptotic mechanisms.
Authors:
Jihane Gasmi; J Thomas Sanderson
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2010-11-10
Journal Detail:
Title:  Journal of agricultural and food chemistry     Volume:  -     ISSN:  1520-5118     ISO Abbreviation:  -     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0374755     Medline TA:  J Agric Food Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Institut National de la Recherche Scientifique, Institut Armand-Frappier, Université du Québec, Laval, Québec H7 V1B7, Canada.
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