Selenium- or quercetin-induced retardation of DNA synthesis in primary prostate cells occurs in the presence of a concomitant reduction in androgen-receptor activity.
Prostate cancer (CaP) is the most common male malignancy in the Western world. Selenium or quercetin may down-regulate prostate-cell proliferation in immortalised cells (e.g. androgen-responsive LNCaP cells). However, whether such effects are apparent in primary prostate epithelial cells (PECs) remains to be examined. Following surgical resection, primary PECs isolated from tissues (n=10 patients) were cultured in the presence or absence of selenium, selenomethionine or quercetin. Tissues from a minimum of three patients were used to generate cell preparations that were cultured independently for the purposes of the experimental analysis of each test agent. These agents were also examined in LNCaP cells. DNA synthesis was assessed by the percentage of PECs or LNCaP cells that incorporated 5-bromo-2-deoxyuridine (BrdU) into DNA. All three test agents induced a dose-related reduction in the percentage of PECs or LNCaP cells labelled with BrdU. In LNCaP cells transfected with an androgen-receptor (AR)-reporter gene coupled to luciferase, selenomethionine or quercetin reduced AR activity. Chemoprevention may retard DNA synthesis in short-term primary PECs and expression of AR-inducible elements may be a concomitant factor.
Morris
Jonathan D H
JD
King's College London, GKT School of Medicine and Dentistry, Rayne Institute, 123 Coldharbour Lane, London SE5 9NU, UK.
Pramanik
Rashida
R
Zhang
Xin
X
Carey
Anne-Marie
AM
Ragavan
Narasimhan
N
Martin
Francis L
FL
Muir
Gordon H
GH
D059002:Androgen Receptor Antagonists; D000975:Antioxidants / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D008297:Male; D011467:Prostate / Q000187:drug effects / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D011794:Quercetin / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000378:metabolism*; D012643:Selenium / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
C410798:AR protein, human; D059002:Androgen Receptor Antagonists; D000975:Antioxidants; D004273:DNA, Neoplasm; D011944:Receptors, Androgen; D011794:Quercetin; D001973:Bromodeoxyuridine; D012643:Selenium