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Effect of Zinc on Prostatic Tumorigenicity in Nude Mice
Author(s) -
FENG PEI,
LI TIE LUO,
GUAN ZHI XIN,
FRANKLIN RENTY B.,
COSTELLO LESLIE C.
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1299.056
Subject(s) - zinc , in vivo , prostate , chemistry , apoptosis , western blot , microbiology and biotechnology , nude mouse , membrane permeability , biology , cancer research , biochemistry , membrane , cancer , organic chemistry , gene , genetics
A bstract : Prostate epithelial cells accumulate the highest zinc levels of any cells in the body. Evidence indicates that zinc plays critical roles in the normal function and pathology of the prostate gland. We have identified two important effects of zinc in the prostate epithelial cells: the inhibition of m‐aconitase and the induction of mitochondrial apoptogenesis. However, at the present time, the effects of zinc on prostatic cells in in vivo conditions have not yet been reported. The objectives of this in vivo study were to investigate the effect of zinc on: tumorogenicity in nude mice, zinc accumulation in tumor tissues, and the levels of mitochondrial membrane permeability related proteins, Bax/Bcl‐2. A tumorigenicity animal model was established using male nude mice (4–6 weeks old) with inoculation of PC‐3 cells (5–10×10 6 /mL) prepared in 10% Matrigel. The mice were treated with zinc by ALZET osmotic pumps (Durect Corporation), with a releasing rate of 0.25 μl/h for 28 days. Zinc concentrations of the tumor tissues were determined by Atomic Absorption Spectrophotometer method. Frozen sections of tumor tissues were prepared for TUNEL assay. The levels of Bax and Bcl‐2 in the tumor tissues were determined by Western blot analyses. Our study demonstrated that in vivo treatment of zinc increased zinc accumulation and citrate production in PC‐3 cell induced tumor tissues and inhibited tumor growth. The inhibitory effect of zinc appears to result from zinc‐induced apoptosis by regulation of mitochondrial membrane permeability‐related Bax/Bcl‐2 proteins.