Effects of Boron Supplementation (Prostate ca)

Effects of boron supplementation on the morphology, PSA levels, and proliferative activity of LNCaP tumors in nude mice

Maria T. Gallardo-Williams, Robert R. Maronpot, Paula E. King, Glenda J. Moser, Thomas L. Goldsworthy, Robert E. Chapin

National Institute of Environmental Health Sciences, Research Triangle Park, NC; ILS, Inc., Research Triangle Park, NC; DuPont Pharmaceuticals Co., Safety Assessment, Newark, DE.

Prostate-specific antigen (PSA) is a serine protease and one of the most abundant proteins secreted by the human prostate epithelium. PSA is used as a well-established marker of prostate cancer. The involvement of PSA in several early events leading to the development of malignant prostate tumors has made it a target for prevention and intervention.

It is thought that PSA cleaves IGFBP, providing increased local levels of IGF, leading to tumor growth. Separately, there are data that suggest an enzymatic regulatory role for dietary boron.

Boron reversibly inhibits several serine proteases. Our own in vitro results suggest that low concentrations (6ėg/mL) of boric acid can partially inhibit the proteolytic activity of purified PSA towards synthetic substrates.

This leads to our hypothesis: dietary supplementation with boric acid will inhibit PSA, which should reduce the development and proliferation of prostate carcinomas. We tested this hypothesis using nude mice implanted subcutaneously with LNCaP cells in Matrigel. Forty male mice were divided into four groups: three groups were dosed with boric acid solutions (1.7, 9.0, and 48.0 mg/kg/day) by gavage. Control group received only water. Tumor sizes were measured weekly. Serum PSA and IGF-1 levels were determined at terminal sacrifice.

The size of tumors was decreased in mice exposed to the low and mid-dose of boric acid by 38% and 25%, respectively. Serum PSA levels decreased by 88.6% and 86.4%, respectively, as compared to the control group.

There were morphological differences between the tumors in control and boron-dosed animals, including a significantly lower incidence of mitotic figures in the boron-supplemented groups. Circulating IGF-1 levels were not different among groups, though immunohistochemical expression of IGF-1 in the tumors was markedly reduced by boron treatment.

These data indicate that low-level dietary B supplementation reduced tumor size and content of a tumor trophic factor, IGF-1. This promising model is being evaluated in further studies.

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