Enhanced Inhibition of Prostate Cancer Xenograft Tumor Growth by Combining Quercetin and Green Tea

J Nutr Biochem. 2014 Jan;25(1):73-80. doi: 10.1016/j.jnutbio.2013.09.005. Epub 2013 Oct 10.

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.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

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

Substances

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