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 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.

Unique natural antioxidants (NAOs) and derived purified components inhibit cell cycle progression by downregulation of ppRb and E2F in human PC3 prostate cancer cells

“…In a more recent study, we elucidated the beneficial effect NAO has in preventing PCA in mice using the TRAMP model [28]. In this model, the efficacy of NAO in reducing the severity of hyperplasia on the various prostate lobes was compared to that of other antioxidants.…”

“…cell proliferation and cell viability Recently, we have elucidated the efficacy of NAO in slowing down the spontaneous tumorigenic progression in TRAMP male mice [28]. The mechanisms involved in the chemopreventive effect of NAO and its purified derived components, are not yet understood.…”

“…This NAO contains polyphenols, which include phenolic acids (p-coumaric acid derivatives) and the glucuronic acid derivatives of flavonoids [26]. We have shown that NAO has antioxidative [26,27], antiproliferative [28], and antiinflammatory properties [29][30][31][32][33] in various biological systems. Spinach flavonoids have been shown to have strong antimutagenic potential and were found beneficial in a Tg.AC mouse model [33].…”

“…The efficacy of NAO was compared to that of the green tea polyphenol, epigallocathecin-3-gallate (EGCG), and N-acetylcysteine (NAC). Although significant effects were exerted on different lobes by the latter three antioxidants, when the most severe hyperplasia in all four lobes of TRAMP mice was evaluated, only NAO reduced hyperplasia at weeks 9 and 13 [28]. In addition, NAO exhibited antiproliferative activity in DU145 and PC3 cells [28].…”

“…Recently, we have investigated the efficacy of NAO in PCA chemoprevention [28]. NAO was tested in the transgenic adenocarcinoma mouse prostate (TRAMP) model.…”