Endocrine-immune-paracrine interactions in prostate cells as targeted by phytomedicines

Nora E. Gray, Xunxian Liu, Renee Choi, Marc R. Blackman, Julia T. Arnold

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Dehydroepiandrosterone (DHEA) is used as a dietary supplement and can be metabolized to androgens and/or estrogens in the prostate. We investigated the hypothesis that DHEA metabolism may be increased in a reactive prostate stroma environment in the presence of proinflammatory cytokines such as transforming growth factor β1 (TGFβ1), and further, whether red clover extract, which contains a variety of compounds including isoflavones, can reverse this effect. LAPC-4 prostate cancer cells were grown in coculture with prostate stromal cells (6S) and treated with DHEA +/- TGFβ1 or interleukin-6. Prostate-specific antigen (PSA) expression and testosterone secretion in LAPC-4/6S cocultures were compared with those in monocultured epithelial and stromal cells by real-time PCR and/or ELISA. Combined administration of TGFβ1 + DHEA to cocultures increased PSA protein secretion two to four times, and PSA gene expression up to 50-fold. DHEA + TGFβ1 also increased coculture production of testosterone over DHEA treatment alone. Red clover isoflavone treatment led to a dose-dependent decrease in PSA protein and gene expression and testosterone metabolism induced by TGFβ1 + DHEA in prostate LAPC-4/6S cocultures. In this coculture model of endocrine-immune-paracrine interactions in the prostate, TGFβ1 greatly increased stromal-mediated DHEA effects on testosterone production and epithelial cell PSA production, whereas red clover isoflavones reversed these effects.

Original languageEnglish (US)
Pages (from-to)134-142
Number of pages9
JournalCancer Prevention Research
Issue number2
StatePublished - Feb 2009
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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