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

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

Research output: Contribution to journalArticle

84 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2324-2331
Number of pages8
JournalPharmaceutical Research
Volume26
Issue number10
DOIs
StatePublished - Oct 2009
Externally publishedYes

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Pharmacodynamics
Pharmacokinetics
Brassica
Transgenic Mice
Prostate
Prostatic Neoplasms
Adenocarcinoma
Phosphotransferases
Apoptosis
Rats
bcl-X Protein
bcl-2-Associated X Protein
Phosphorylation
Oral Administration
Cyclin D1
Tumor Biomarkers
TOR Serine-Threonine Kinases
Caspase 3
Glutathione
Tumors

Keywords

  • Broccoli sprout
  • Nrf2
  • Prostate cancer
  • Sulforaphane
  • TRAMP mice

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Organic Chemistry
  • Molecular Medicine
  • Pharmacology (medical)
  • Biotechnology
  • Pharmacology

Cite this

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

In: Pharmaceutical Research, Vol. 26, No. 10, 10.2009, p. 2324-2331.

Research output: Contribution to journalArticle

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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.",
keywords = "Broccoli sprout, Nrf2, Prostate cancer, Sulforaphane, TRAMP mice",
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AU - Keum, Young Sam

AU - Oo Khor, Tin

AU - Lin, Wen

AU - Shen, Guoxiang

AU - Han Kwon, Ki

AU - Barve, Avantika

AU - Li, Wenge

AU - Kong, Ah Ng

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N2 - 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.

AB - 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.

KW - Broccoli sprout

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KW - Sulforaphane

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