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Pomegranate and its polyphenols downregulate gene expression of androgen synthesizing enzymes in human prostate cancer cells overexpressing the androgen receptor
Author(s) -
Hong Mee Young,
Seeram Navindra P.,
Heber David
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.702.3
Subject(s) - lncap , androgen receptor , prostate cancer , androgen , downregulation and upregulation , cancer research , chemistry , biology , endocrinology , medicine , cancer , gene , biochemistry , hormone
Early stage prostate cancer (PCa) is treatable, but recurrence after primary treatment with development of androgen‐independent (AI) PCa metastases can lead to death. Therefore, prevention of the development of AI PCa is critical to reducing overall prostate cancer mortality. Cellular adaptations during development of AI include increased androgen receptor (AR) expression and increased intracellular androgen synthesis accounting for resistance to castration in AI PCa. In this study, we examined the effects of Pomegranate (POM) extract and a whole POM juice extract on the expression of genes for key androgen synthesizing enzymes and AR. Expression of the HSD3B2, AKR1C3 and SRD5A1 genes for androgen synthesizing enzymes were determined by real time PCR in LNCaP, LNCaP‐AR, and DU‐145 human prostate cancer cells in vitro. Pomegranate and its polyphenols decreased tumor cell proliferation (P<0.01) in all three cell types. Pomegranate polyphenols also inhibited expression of genes for androgen synthesizing enzymes and AR more than two‐fold most consistently in the androgen independent LNCaP‐AR cell line (P<0.05). Therefore, the effects of pomegranate polyphenols may be mediated in part by inhibition of androgen synthesizing enzymes in PCa when AR is upregulated in AI PCa. Supported by UCLA CNRU CA 42710 and DOD W81XWH‐07‐1‐0158.