Enhanced inhibition of prostate cancer xenograft tumor growth by combining quercetin and green tea.

Abstract

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.

• Authors: Piwen Wang, Jaydutt V Vadgama, Jonathan W Said, Clara E Magyar, Ngan Doan, David Heber, Susanne M Henning
• Journal: The Journal of nutritional biochemistry (J Nutr Biochem) Vol. 25 Issue 1 Pg. 73-80 (Jan 2014) ISSN: 1873-4847 [Electronic] United States
• PMID: 24314868 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2014.

Chemical References

• Antineoplastic Agents
• Multidrug Resistance-Associated Proteins
• Polyphenols
• Receptors, Androgen
• Tea
• Quercetin
• Catechol O-Methyltransferase
• Phosphatidylinositol 3-Kinases
• multidrug resistance-associated protein 1

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Catechol O-Methyltransferase (genetics, metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Chemoprevention
• Male
• Mice
• Mice, SCID
• Multidrug Resistance-Associated Proteins (genetics, metabolism)
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Polyphenols (pharmacology)
• Prostatic Neoplasms (drug therapy, pathology)
• Quercetin (pharmacology)
• Receptors, Androgen (metabolism)
• Tea (chemistry)
• Xenograft Model Antitumor Assays