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Slowing Tumorigenic Progression in TRAMP Mice and Prostatic Carcinoma Cell Lines Using Natural Anti-Oxidant from Spinach, NAO—A Comparative Study of Three Anti-Oxidants

Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina 27709, nyska{at}niehs.nih.gov

Andrew Suttie

Integrated Laboratory Systems (ILS), Research Triangle Park, North Carolina 27709, USA

Shlomo Bakshi

Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel

Liat Lomnitski

Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel

Sholomo Grossman

Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel

Margalit Bergman

Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel

Varda Ben-Shaul

Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel

Patrick Crocket

Analytical Sciences, Inc, Durham, North Carolina 27713, USA

Joseph K. Haseman

Biostatistics Branch, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina 27709

Glenda Moser

Integrated Laboratory Systems (ILS), Research Triangle Park, North Carolina 27709, USA

Thomas L. Goldsworthy

Integrated Laboratory Systems (ILS), Research Triangle Park, North Carolina 27709, USA

Robert R. Maronpot

Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina 27709

The TRAMP model and human prostatic cancer (PCA) cell lines DU145 and PC3 are useful for chemopreventive studies. We compared the efficacy of 3 anti-oxidants [a water-soluble natural anti-oxidant, NAO (200 mg/kg), found in spinach leaves; epigallocatechin-3 gallate, EGCG (200 mg/kg), a major green tea polyphenol; and N-acetylcysteine, NAC (125 mg/kg)] plus vehicle in slowing spontaneous tumorigenic progression in TRAMP and wild-type male mice. Sacrifices occurred on weeks 5, 9, and 13. Prostatic histopathology and oxidative-stress blood markers were evaluated. Hyperplasias were ranked by a combination of severity grade and distribution (focal, multifocal, and diffuse). The effectivity of each tested compound in reducing the severity/focalness of hyperplasia varied from lobe to lobe. NAO exerted a significant effect on the dorsal and lateral lobes; NAC, on the anterior and ventral lobes, and EGCG, on the ventral lobe. When the most severe hyperplasia in all 4 lobes of TRAMPs was evaluated, only NAO reduced hyperplasia at weeks 9 and 13. Plasma peroxide levels in TRAMPs were reduced following oral administration of NAO or NAC for 13 weeks; EGCG only slightly reduced these levels. In NAO-treated DU145 and PC3 PCA cells, inhibition of cellular proliferation occurred in a dose-dependent manner, increasing numbers of G1 cells and reducing ROS levels. The anti-oxidative and antiproliferative properties of NAO may explain its efficacy in slowing the spontaneous prostatic carcinogenic process in the TRAMP and its effects in the cell lines.

Key Words: Anti-oxidant • spinach • TRAMP mice • prostate • hyperplasia • cancer.

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Toxicologic Pathology, Vol. 31, No. 1, 39-51 (2003)
DOI: 10.1080/01926230390173833


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