Ursolic acid and its esters: occurrence in cranberries and other Vaccinium fruit and effects on matrix metalloproteinase activity in DU145 prostate tumor cells

Authors

  • Miwako Kondo,

    1. Department of Chemistry and Biochemistry, University of Massachusetts Dartmouth, North Dartmouth, MA 02747, USA
    Current affiliation:
    1. Brunswick Laboratories, Norton, MA 02766, USA.
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  • Shawna L MacKinnon,

    1. Institute for Marine Biosciences, National Research Council of Canada, Halifax, Nova Scotia B3H 3Z1, Canada
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  • Cheryl C Craft,

    1. Institute for Marine Biosciences, National Research Council of Canada, Halifax, Nova Scotia B3H 3Z1, Canada
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  • Michael D Matchett,

    1. Department of Biology, University of Prince Edward Island, Charlottetown, Prince Edward Island C1A 4P3, Canada
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  • Robert A R Hurta,

    1. Department of Biology, University of Prince Edward Island, Charlottetown, Prince Edward Island C1A 4P3, Canada
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  • Catherine C Neto

    Corresponding author
    1. Department of Chemistry and Biochemistry, University of Massachusetts Dartmouth, North Dartmouth, MA 02747, USA
    • Department of Chemistry and Biochemistry, University of Massachusetts Dartmouth, North Dartmouth, MA 02747, USA.
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Abstract

BACKGROUND: Ursolic acid and its cis- and trans-3-O-p-hydroxycinnamoyl esters have been identified as constituents of American cranberries (Vaccinium macrocarpon), which inhibit tumor cell proliferation. Since the compounds may contribute to berry anticancer properties, their content in cranberries, selected cranberry products, and three other Vaccinium species (V. oxycoccus, V. vitis-idaea and V. angustifolium) was determined by liquid chromatography-mass spectroscopy. The ability of these compounds to inhibit growth in a panel of tumor cell lines and inhibit matrix metalloproteinase (MMP) activity associated with tumor invasion and metastasis was determined in DU145 prostate tumor cells.

RESULTS: The highest content of ursolic acid and esters was found in V. macrocarpon berries (0.460–1.090 g ursolic acid and 0.040–0.160 g each ester kg−1 fresh weight). V. vitis-idaea and V. angustifolium contained ursolic acid (0.230–0.260 g kg−1), but the esters were not detected. V. oxycoccus was lowest (0.129 g ursolic acid and esters per kg). Ursolic acid content was highest in cranberry products prepared from whole fruit. Ursolic acid and its esters inhibited tumor cell growth at micromolar concentrations, and inhibited MMP-2 and MMP-9 activity at concentrations below those previously reported for cranberry polyphenolics.

CONCLUSION: Cranberries (V. macrocarpon) were the best source of ursolic acid and its esters among the fruit and products tested. These compounds may limit prostate carcinogenesis through matrix metalloproteinase inhibition. Copyright © 2011 Society of Chemical Industry

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