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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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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.

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Acknowledgement

We thank Mr. Richard Jarrell for providing us with the broccoli sprouts. We thank all the members in Dr. Ah-Ng “Tony” Kong’s lab for the help in discussion and preparation of this manuscript. This work was supported in part by the National Institute of Health Grant R01-CA118947 and Institutional Funds.

Author information

Author notes

  1. Wen Lin

    Present address: Novartis Institutes for BioMedical Research, DMPK-Translational Sciences (TS), East Hanover, New Jersey, 07936, USA

  2. Guoxiang Shen

    Present address: Metabolism and Pharmacokinetics, Research & Development Bristol- Myers Squibb Co, Princeton, New Jersey, 08543, USA

  3. Avantika Barve

    Present address: Bioanalytical R & D, Wyeth Pharmaceuticals, 401 N Middletown Rd, Pearl River, New York, 10965, USA

Authors and Affiliations

  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

    Young-Sam Keum, Tin Oo Khor, Wen Lin, Guoxiang Shen, Ki Han Kwon, Avantika Barve, Wenge Li & Ah-Ng Kong

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  1. Young-Sam Keum
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  2. Tin Oo Khor
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Correspondence to Ah-Ng Kong.

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Keum, YS., Oo Khor, T., Lin, W. et al. 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. Pharm Res 26, 2324–2331 (2009). https://doi.org/10.1007/s11095-009-9948-5

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  • DOI: https://doi.org/10.1007/s11095-009-9948-5

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