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.
OBJECTIVE
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.
Keum
Young-Sam
YS
Department of Pharmaceutics and Ernest Mario School of Pharmacy, Rutgers The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey 08854, USA.
Khor
Tin Oo
TO
Lin
Wen
W
Shen
Guoxiang
G
Kwon
Ki Han
KH
Barve
Avantika
A
Li
Wenge
W
Kong
Ah-Ng
AN
D000230:Adenocarcinoma / Q000178:diet therapy / Q000378:metabolism* / Q000517:prevention & control; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001937:Brassica; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis*; D010936:Plant Extracts / Q000493:pharmacokinetics / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000178:diet therapy / Q000378:metabolism* / Q000517:prevention & control; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012639:Seeds; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D010936:Plant Extracts; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D051057:Proto-Oncogene Proteins c-akt