Modest induction of phase 2 enzyme activity in the F-344 rat prostate.
BACKGROUND
Prostate cancer is the most commonly diagnosed malignancy in men and is thought to arise as a result of endogenous oxidative stress in the face of compromised carcinogen defenses. We tested whether carcinogen defense (phase 2) enzymes could be induced in the prostate tissues of rats after oral feeding of candidate phase 2 enzyme inducing compounds.


METHODS
Male F344 rats were gavage fed sulforaphane, beta-naphthoflavone, curcumin, dimethyl fumarate or vehicle control over five days, and on the sixth day, prostate, liver, kidney and bladder tissues were harvested. Cytosolic enzyme activities of nicotinamide quinone oxidoreductase (NQO1), total glutathione transferase (using DCNB) and mu-class glutathione transferase (using CDNB) were determined in the treated and control animals and compared.


RESULTS
In prostatic tissues, sulforaphane produced modest but significant increases in the enzymatic activities of NQO1, total GST and GST-mu compared to control animals. beta-naphthoflavone significantly increased NQO1 and GST-mu activities and curcumin increased total GST and GST-mu enzymatic activities. Dimethyl fumarate did not significantly increase prostatic phase 2 enzyme activity. Compared to control animals, sulforaphane also significantly induced NQO1 or total GST enzyme activity in the liver, kidney and, most significantly, in the bladder tissues. All compounds were well tolerated over the course of the gavage feedings.


CONCLUSIONS
Orally administered compounds will induce modestly phase 2 enzyme activity in the prostate although the significance of this degree of induction is unknown. The 4 different compounds also altered phase 2 enzyme activity to different degrees in different tissue types. Orally administered sulforaphane potently induces phase 2 enzymes in bladder tissues and should be investigated as a bladder cancer preventive agent.
Jones
Sunita B
SB
Department of Urology, Stanford University School of Medicine, Stanford, California 94305, USA. subjns@yahoo.com
Brooks
James D
JD
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology; D000069462:Dimethyl Fumarate; D005650:Fumarates / Q000494:pharmacology; D005982:Glutathione Transferase / Q000378:metabolism; D017879:Isothiocyanates; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D011467:Prostate / Q000187:drug effects* / Q000201:enzymology*; D051381:Rats; D011916:Rats, Inbred F344; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000201:enzymology; D019324:beta-Naphthoflavone / Q000494:pharmacology
D016588:Anticarcinogenic Agents; D005650:Fumarates; D017879:Isothiocyanates; D013454:Sulfoxides; D013861:Thiocyanates; D019324:beta-Naphthoflavone; D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat; D005982:Glutathione Transferase; D000069462:Dimethyl Fumarate; C016766:sulforaphane; D003474:Curcumin