title: Green tea and quercetin sensitize PC-3 xenograft prostate tumors to docetaxel chemotherapy.
abstract: BACKGROUND
  Chemotherapy with docetaxel (Doc) remains the standard treatment for metastatic and castration-resistance prostate cancer (CRPC). However, the clinical success of Doc is limited by its chemoresistance and side effects. This study investigated whether natural products green tea (GT) and quercetin (Q) enhance the therapeutic efficacy of Doc in CRPC in mouse models.
  
  
  METHODS
  Male severe combined immunodeficiency (SCID) mice (n = 10 per group) were inoculated with androgen-independent prostate cancer PC-3 cells subcutaneously. When tumors were established the intervention started. Mice were administered with GT + Q, Doc 5 mg/kg (LD), GT + Q + LD Doc, Doc 10 mg/kg (HD) or control. The concentration of GT polyphenols in brewed tea administered as drinking water was 0.07% and Q was supplemented in diet at 0.4%. Doc was intravenously injected weekly for 4 weeks, GT and Q given throughout the study.
  
  
  RESULTS
  GT + Q or LD Doc slightly inhibited tumor growth compared to control. However, the combination of GT and Q with LD Doc significantly enhanced the potency of Doc 2-fold and reduced tumor growth by 62% compared to LD Doc in 7-weeks intervention. A decrease of Ki67 and increase of cleaved caspase 7 were observed in tumors by the mixture, along with lowered blood concentrations of growth factors like VEGF and EGF. The mixture significantly elevated the levels of tumor suppressor mir15a and mir330 in tumor tissues. An increased risk of liver toxicity was only observed with HD Doc treatment.
  
  
  CONCLUSIONS
  These results provide a promising regimen to enhance the therapeutic effect of Doc in a less toxic manner.
authors.affiliation: Division of Cancer Research and Training, Charles R. Drew University of Medicine and Science, Los Angeles, CA, 90059, USA. piwenwang@cdrewu.edu.|Center for Human Nutrition, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA. piwenwang@cdrewu.edu.
authors.forename: Piwen
authors.initials: P
authors.lastname: Wang
authors.affiliation: Center for Human Nutrition, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Henning
authors.affiliation: Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
authors.forename: Clara E
authors.initials: CE
authors.lastname: Magyar
authors.affiliation: Division of Cancer Research and Training, Charles R. Drew University of Medicine and Science, Los Angeles, CA, 90059, USA.
authors.forename: Yahya
authors.initials: Y
authors.lastname: Elshimali
authors.affiliation: Center for Human Nutrition, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
authors.forename: David
authors.initials: D
authors.lastname: Heber
authors.affiliation: Division of Cancer Research and Training, Charles R. Drew University of Medicine and Science, Los Angeles, CA, 90059, USA.|Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
authors.forename: Jaydutt V
authors.initials: JV
authors.lastname: Vadgama
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D059808:Polyphenols / Q000008:administration & dosage* / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011794:Quercetin / Q000008:administration & dosage* / Q000494:pharmacology; D043823:Taxoids / Q000008:administration & dosage* / Q000494:pharmacology; D013662:Tea / Q000737:chemistry*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D010936:Plant Extracts; D059808:Polyphenols; D043823:Taxoids; D013662:Tea; D000077143:Docetaxel; D011794:Quercetin
keywords: Combination; Docetaxel; Green tea polyphenol; Prostate cancer; Quercetin