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.
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.
Nyska
Abraham
A
Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina 27709, USA. nyska@niehs.nih.gov
Suttie
Andrew
A
Bakshi
Shlomo
S
Lomnitski
Liat
L
Grossman
Sholomo
S
Bergman
Margalit
M
Ben-Shaul
Varda
V
Crocket
Patrick
P
Haseman
Joseph K
JK
Moser
Glenda
G
Goldsworthy
Thomas L
TL
Maronpot
Robert R
RR
D000111:Acetylcysteine / Q000302:isolation & purification / Q000627:therapeutic use; D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000302:isolation & purification / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D018450:Disease Progression; D004354:Drug Screening Assays, Antitumor; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011470:Prostatic Hyperplasia / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D018724:Spinacia oleracea / Q000737:chemistry*; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D017382:Reactive Oxygen Species; D002392:Catechin; C045651:epigallocatechin gallate; D000111:Acetylcysteine