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.

Abstract

The TRAMP model and human prostatic cancer (PCA) cell lines DU145 and PC3 are useful forchemopreventive 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 DU 145 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.

• Authors: Abraham Nyska, Andrew Suttie, Shlomo Bakshi, Liat Lomnitski, Sholomo Grossman, Margalit Bergman, Varda Ben-Shaul, Patrick Crocket, Joseph K Haseman, Glenda Moser, Thomas L Goldsworthy, Robert R Maronpot
• Journal: Toxicologic pathology (Toxicol Pathol) 2003 Jan-Feb Vol. 31 Issue 1 Pg. 39-51 ISSN: 0192-6233 [Print] United States
• PMID: 12597448 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Reactive Oxygen Species
• Catechin
• epigallocatechin gallate
• Acetylcysteine

Topics

• Acetylcysteine (isolation & purification, therapeutic use)
• Administration, Oral
• Animals
• Antioxidants (isolation & purification, therapeutic use)
• Carcinoma (drug therapy, metabolism, pathology)
• Catechin (analogs & derivatives, isolation & purification, therapeutic use)
• Cell Division (drug effects)
• Disease Progression
• Drug Screening Assays, Antitumor
• G1 Phase (drug effects)
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Prostatic Hyperplasia (metabolism, pathology)
• Prostatic Neoplasms (drug therapy, metabolism, pathology)
• Reactive Oxygen Species (metabolism)
• Spinacia oleracea (chemistry)
• Tumor Cells, Cultured