Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Selenium- or quercetin-induced retardation of DNA synthesis in primary prostate cells occurs in the presence of a concomitant reduction in androgen-receptor activity.
AU - Morris, Jonathan D.
AU - Pramanik, Rashida
AU - Zhang, Xin
AU - Carey, Anne Marie
AU - Ragavan, Narasimhan
AU - Martin, Francis L.
AU - Muir, Gordon H.
PY - 2006/7/28
Y1 - 2006/7/28
N2 - 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.
AB - 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.
KW - Androgen receptor
KW - Luciferase-reporter gene
KW - LNCaP cells
KW - Prostate cancer
KW - Prostate epithelial cells
KW - Quercetin
KW - Selenium
U2 - 10.1016/j.canlet.2005.07.037
DO - 10.1016/j.canlet.2005.07.037
M3 - Journal article
VL - 239
SP - 111
EP - 122
JO - Cancer Letters
JF - Cancer Letters
SN - 0304-3835
IS - 1
ER -