title: 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: Division of Cancer Research and Training, Charles R. Drew University of Medicine and Science, Los Angeles, CA, 90059, USA; Center for Human Nutrition, University of California, Los Angeles, CA, 90095, USA. Electronic address: piwenwang@cdrewu.edu.
authors: Piwen
authors: P
authors: Wang
authors: Jaydutt V
authors: JV
authors: Vadgama
authors: Jonathan W
authors: JW
authors: Said
authors: Clara E
authors: CE
authors: Magyar
authors: Ngan
authors: N
authors: Doan
authors: David
authors: D
authors: Heber
authors: Susanne M
authors: SM
authors: Henning
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002394:Catechol O-Methyltransferase / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018890:Chemoprevention; D008297:Male; D051379:Mice; D016513:Mice, SCID; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D059808:Polyphenols / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011794:Quercetin / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000378:metabolism; D013662:Tea / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D002394:Catechol O-Methyltransferase; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D019869:Phosphatidylinositol 3-Kinases; D059808:Polyphenols; D011794:Quercetin; D011944:Receptors, Androgen; D013662:Tea; C421109:multidrug resistance-associated protein 1
keywords: 4″-MeEGCG; 4″-O-methyl EGCG; AR; COMT; Catechol-O-methyltransferase; EC, (−)-epicatechin; ECG, (−)-epicatechin-3-gallate; EGC; EGCG, (−); GT; GTPs; Green tea; HD; HPLC; LD; MRP; PI3K; PSA; Prostate cancer; Q; Quercetin; SCID; SCID mice; androgen receptor; catechol-O-methyltransferase; epigallocatechin; epigallocatechin-3-gallate; green tea; green tea polyphenols; high dose; high-performance liquid chromatography; low dose; mTOR; mammalian target of rapamycin; multidrug resistance-associated protein; phosphatidylinositol 3-kinases; prostate-specific antigen; quercetin; severe combined immunodeficiency