TY - JOUR
T1 - 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
AU - Nyska, Abraham
AU - Suttie, Andrew
AU - Bakshi, Shlomo
AU - Lomnitski, Liat
AU - Grossman, Sholomo
AU - Bergman, Margalit
AU - Ben-Shaul, Varda
AU - Crocket, Patrick
AU - Haseman, Joseph K.
AU - Moser, Glenda
AU - Goldsworthy, Thomas L.
AU - Maronpot, Robert R.
PY - 2003/1
Y1 - 2003/1
N2 - 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.
AB - 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.
KW - Anti-oxidant
KW - TRAMP mice
KW - cancer
KW - hyperplasia
KW - prostate
KW - spinach
UR - http://www.scopus.com/inward/record.url?scp=12244310450&partnerID=8YFLogxK
U2 - 10.1080/01926230390173833
DO - 10.1080/01926230390173833
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C2 - 12597448
AN - SCOPUS:12244310450
SN - 0192-6233
VL - 31
SP - 39
EP - 51
JO - Toxicologic Pathology
JF - Toxicologic Pathology
IS - 1
ER -