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Growth inhibitory, antiandrogenic, and pro-apoptotic effects of punicic acid in LNCaP human prostate cancer cells

Gasmi, Jihane et Sanderson, J. Thomas ORCID logoORCID: https://orcid.org/0000-0002-3190-2811 (2010). Growth inhibitory, antiandrogenic, and pro-apoptotic effects of punicic acid in LNCaP human prostate cancer cells Journal of Agricultural and Food Chemistry , vol. 58 , nº 23. pp. 12149-12156. DOI: 10.1021/jf103306k.

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Résumé


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.

Type de document: Article
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Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 30 juin 2024 18:02
Dernière modification: 30 juin 2024 18:02
URI: https://espace.inrs.ca/id/eprint/14687

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