Journal
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
Volume 25, Issue 1, Pages 73-80Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2013.09.005
Keywords
Green tea; Quercetin; Prostate cancer; Catechol-O-methyltransferase; SCID mice
Funding
- NATIONAL CANCER INSTITUTE [R03CA150047, P30CA016042, U54CA143931, P50CA092131, R01CA116242] Funding Source: NIH RePORTER
- NCI NIH HHS [R01 CA116242, U54 CA143931, R03 CA150047, U54 CA143931-01, P50CA092131, R03 CA150047-01, P50 CA092131, P30 CA016042] Funding Source: Medline
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The chemopreventive activity of green tea (GT) is limited by the low bioavailability and extensive methylation of GT polyphenols (GTPs) in vivo. We determined whether a methylation inhibitor quercetin (Q) will enhance the chemoprevention of prostate cancer in vivo. Androgen-sensitive LAPC-4 prostate cancer cells were injected subcutaneously into severe combined immunodeficiency (SCID) mice one week before the intervention. The concentration of GTPs in brewed tea administered as drinking water was 0.07% and Q was supplemented in diet at 0.2% or 0.4%. After 6-weeks of intervention tumor growth was inhibited by 3% (0.2% Q), 15% (0.4% Q), 21% (GT), 28% (GT+0.2% Q) and 45% (GT+0.4% Q) compared to control. The concentration of non-methylated GTPs was significantly increased in tumor tissue with GT+0.4% Q treatment compared to GT alone, and was associated with a decreased protein expression of catechol-O-methyltransferase and multidrug resistance-associated protein (MRP)-1. The combination treatment was also associated with a significant increase in the inhibition of proliferation, androgen receptor and phosphatidylinositol 3-kinase/Akt signaling, and stimulation of apoptosis. The combined effect of GT+0.4% Q on tumor inhibition was further confirmed in another experiment where the intervention started prior to tumor inoculation. These results provide a novel regimen by combining GT and Q to improve chemoprevention in a non-toxic manner and warrant future studies in humans. (C) 2014 Elsevier Inc. All rights reserved.
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