Conflicting Influence of Dietary Supplements on Prostate Cancer

National Institutes of Health (Bethesda, MD, USA) worked with a "coculture” system in which LAPC-4 prostate cancer cells were grown together with underlying prostate stromal cells (6S). The cultures were treated with DHEA alone or together with the proinflammatory cytokine, transforming growth factor beta-1 (TGF-beta-1). Following that treatment, some cultures were further treated with an extract of red clover, a rich source of isoflavones. Prostate-specific antigen (PSA) expression and testosterone secretion in LAPC-4/6S cocultures were compared with those in epithelial and stromal cell monocultures by real-time polymerase chain reaction (PCR) and/or enzyme-linked immunosorbent assay (ELISA).

Results published in the January 13, 2009, online edition of the journal Cancer Prevention Research revealed that combined administration of TGF-beta-1 and DHEA to cocultures increased PSA protein secretion two to four times, and PSA gene expression up to 50-fold. DHEA combined with TGF-beta-1 also increased coculture production of testosterone over DHEA treatment alone. Red clover isoflavone treatment led to a dose-dependent decrease in PSA protein, gene expression, and testosterone metabolism induced by TGF-beta-1 plus DHEA in prostate LAPC-4/6S cocultures.

"DHEA effects in the prostate tissues may depend on how these two cells types ‘talk to each other' and further, it may be potentially harmful in tissues containing inflammation or with early cancer lesions because the cells can induce DHEA to become more androgenic,” said senior author Dr. Julie Arnold, a staff scientist at the National Institutes of Health. "Something is happening in the prostate tissue microenvironment that is illustrating a potential cancer prevention effect from the [red clover extract] supplement.”

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