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Pharm Res. 2009 Oct;26(10):2324-31. doi: 10.1007/s11095-009-9948-5. Epub 2009 Aug 8.

Pharmacokinetics and pharmacodynamics of broccoli sprouts on the suppression of prostate cancer in transgenic adenocarcinoma of mouse prostate (TRAMP) mice: implication of induction of Nrf2, HO-1 and apoptosis and the suppression of Akt-dependent kinase pathway.

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1
Department of Pharmaceutics and Ernest Mario School of Pharmacy, Rutgers The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey 08854, USA.

Abstract

PURPOSE:

In the present study, we have evaluated the pharmacokinetics and the in vivo prostate chemopreventive activity of broccoli sprouts.

METHODS:

The in vivo pharmacokinetic profiles of sulforaphane (SFN) and SFN- glutathione (GSH) conjugate in rats after oral administration of 200 mg and 500 mg broccoli sprouts were analyzed. Next, 8-week old TRAMP mice were fed with dietary broccoli sprouts at two dosages (60 and 240 mg/mouse/day) for 16 weeks, and the mice were sacrificed to examine the pharmacodynamic response on prostate tumor and some biomarkers.

RESULTS:

SFN was readily released and conjugated with GSH in the rats after oral administration of broccoli sprouts. TRAMP mice fed with 240 mg broccoli sprouts/mouse/day exhibited a significant retardation of prostate tumor growth. Western blot analysis revealed that the expression levels of Nrf2, HO-1, cleaved-Caspase-3, cleaved-PARP and Bax proteins were increased, but that of Keap1 and Bcl-XL proteins were decreased. In addition, the phosphorylation and/or the expression level of Akt and its downstream kinase and target proteins, e.g. mTOR, 4E-BP1 and cyclin D1, were reduced.

CONCLUSIONS:

Our findings indicate that broccoli sprouts can serve as a good dietary source of SFN in vivo and that they have significant inhibitory effects on prostate tumorigenesis.

PMID:
19669099
DOI:
10.1007/s11095-009-9948-5
[Indexed for MEDLINE]

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