Pomegranate extract inhibits androgen-independent prostate cancer growth through a nuclear factor-kappaB-dependent mechanism.
Constitutive nuclear factor-kappaB (NF-kappaB) activation is observed in androgen-independent prostate cancer and represents a predictor for biochemical recurrence after radical prostatectomy. Dietary agents such as pomegranate extract (PE) have received increasing attention as potential agents to prevent the onset or progression of many malignancies, including prostate cancer. Here, we show that PE inhibited NF-kappaB and cell viability of prostate cancer cell lines in a dose-dependent fashion in vitro. Importantly, maximal PE-induced apoptosis was dependent on PE-mediated NF-kappaB blockade. In the LAPC4 xenograft model, PE delayed the emergence of LAPC4 androgen-independent xenografts in castrated mice through an inhibition of proliferation and induction of apoptosis. Moreover, the observed increase in NF-kappaB activity during the transition from androgen dependence to androgen independence in the LAPC4 xenograft model was abrogated by PE. Our study represents the first description of PE as a promising dietary agent for the prevention of the emergence of androgen independence that is driven in part by heightened NF-kappaB activity.
Rettig
Matthew B
MB
Department of Medicine, Division of Hematology-Oncology, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA, USA. mrettig@mednet.ucla.edu
Heber
David
D
An
Jiabin
J
Seeram
Navindra P
NP
Rao
Jian Y
JY
Liu
Huiren
H
Klatte
Tobias
T
Belldegrun
Arie
A
Moro
Aune
A
Henning
Susanne M
SM
Mo
Deqiong
D
Aronson
William J
WJ
Pantuck
Allan
A
D000728:Androgens / Q000378:metabolism; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D029561:Lythraceae / Q000378:metabolism*; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D000728:Androgens; D016328:NF-kappa B; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha
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