%0 Journal Article %~ Pubmed %A Singh, Jaskirat %A Xie, Chanlu %A Yao, Mu %A Hua, Sheng %A Vignarajan, Soma %A Jardine, Greg %A Hambly, Brett D %A Sved, Paul %A Dong, Qihan %T Food extracts consumed in Mediterranean countries and East Asia reduce protein concentrations of androgen receptor, phospho-protein kinase B, and phospho-cytosolic phospholipase A(2)alpha in human prostate cancer cells. %B The Journal of nutrition %D 2010 %V 140 %N 4 %P 786-91 %@ 1541-6100 %X Active surveillance is an emerging management option for the rising number of men with low-grade, clinically localized prostate cancer. However, 30-40% of men on active surveillance will progress to high-grade disease over 5 y. With the ultimate aim of developing a food-based chemoprevention strategy to retard cancer progression in these otherwise healthy men, we have developed a blend of food extracts commonly consumed in Mediterranean countries and East Asia. The effect of the food extracts known as Blueberry Punch (BBP) on prostate cancer cell growth and key signaling pathways were examined in vitro and in vivo. BBP reduced prostate cancer cell growth in a dose-dependent manner (0.08-2.5%) at 72 h in vitro due to the reduction in cell proliferation and viability. Prostate cancer cell xenograft-bearing mice, administered 10% BBP in drinking water for 2 wk, had a 25% reduction in tumor volume compared with the control (water only). In vitro, BBP reduced protein concentrations in 3 signaling pathways necessary for the proliferation and survival of prostate cancer cells, namely androgen receptor, phospho-protein kinase B/protein kinase B, and phospho-cytosolic phospholipase A(2)alpha. The downstream effectors of these pathways, including prostate-specific antigen and glycogen synthase kinase 3beta, were also reduced. Thus, this palatable food supplement is a potential candidate for testing in clinical trials and may ultimately prove effective in retarding the progression of low-grade, early-stage prostate cancer in men managed by active surveillance. %Z FOR Codes: 111201 %0 Journal Article %~ Pubmed %A Patel, Manish I %A Singh, Jaskirat %A Niknami, Marzieh %A Kurek, Caroline %A Yao, Mu %A Lu, Sasa %A Maclean, Fiona %A King, Nicholas J C %A Gelb, Michael H %A Scott, Kieran F %A Russell, Pamela J %A Boulas, John %A Dong, Qihan %T Cytosolic Phospholipase A2-{alpha}: A Potential Therapeutic Target for Prostate Cancer. %B Clinical Cancer Research %D 2008 %V 14 %N 24 %P 8070-9 %@ 1078-0432 %X PURPOSE: Cytosolic phospholipase A2-alpha (cPLA(2)-alpha) provides intracellular arachidonic acid to supply both cyclooxygenase and lipoxygenase pathways. We aim to determine the expression and activation of cPLA(2)-alpha in prostate cancer cell lines and tissue and the effect of targeting cPLA(2)-alpha in vitro and in vivo. EXPERIMENTAL DESIGN: The expression of cPLA(2)-alpha was determined in prostate cancer cells by reverse transcription-PCR, Western blot, and immunocytochemistry. Growth inhibition, apoptosis, and cPLA(2)-alpha activity were determined after inhibition with cPLA(2)-alpha small interfering RNA or inhibitor (Wyeth-1). Cytosolic PLA(2)-alpha inhibitor or vehicle was also administered to prostate cancer xenograft mouse models. Finally, the expression of phosphorylated cPLA(2)-alpha was determined by immunohistochemistry in human normal, androgen-sensitive and androgen-insensitive prostate cancer specimens. RESULTS: cPLA(2)-alpha is present in all prostate cancer cells lines, but increased in androgen-insensitive cells. Inhibition with small interfering RNA or Wyeth-1 results in significant reductions in prostate cancer cell numbers, as a result of reduced proliferation as well as increased apoptosis, and this was also associated with a reduction in cPLA(2)-alpha activity. Expression of cyclin D1 and phosphorylation of Akt were also observed to decrease. Wyeth-1 inhibited PC3 xenograft growth by approximately 33% and again, also reduced cyclin D1. Immunohistochemistry of human prostate tissue revealed that phosphorylated cPLA(2)-alpha is increased when hormone refractory is reached. CONCLUSIONS: Expression and activation of cPLA(2)-alpha are increased in the androgen-insensitive cancer cell line and tissue. Inhibition of cPLA(2)-alpha results in cells and xenograft tumor growth inhibition and serves as a potentially effective therapy for hormone refractory prostate cancer. %Z FOR Codes: 111201 %0 Journal Article %~ Pubmed %A Singh, Jaskirat %A Young, Lei %A Handelsman, David J %A Dong, Qihan %T Molecular cloning and characterization of a novel androgen repressible gene expressed in the prostate epithelium. %B Gene %D 2005 %V 348 %N %P 55-63 %@ 0378-1119 %X Prostate cancer deaths are due to functional escape of prostate cancer cells from their original androgen-dependent growth. To better understand the origin and evolution of hormone-refractory prostate cancer, it is important to identify and characterize genes expressed in the androgen-deprived prostate. We have verified that the rudimentary prostate of congenital androgen deficient mice (hpg) is indeed androgen independent. Using suppression subtractive hybridization between mRNA derived from prostates of hypogonadal (hpg) with or without 14 days of testosterone replacement we have cloned a novel gene from the hpg prostate, termed ADMP (for androgen down regulated gene expressed in mouse prostate), that is down regulated by androgens. ADMP expression is strong in hpg mouse prostate, weak in mature castrated mouse prostate and absent in normal intact or androgen-replaced hpg mouse prostates. While ADMP expression is androgen independent in the hpg prostate, it appears to be androgen-dependent in the kidney and brain of normal intact mouse suggesting tissue specific regulation of ADMP by androgens. Human ADMP mRNA expression is suppressed by androgens in the androgen-sensitive LNCaP cell line. The predicted mouse and human protein of 76 amino acids shares sequence similarity to a putative G-protein coupled receptor indicating its possible role in signal transduction. Human ADMP expression was seen predominantly in the prostate epithelium with weaker expression in the fibroblasts and endothelial cells. Cloning and characterization of ADMP has made it feasible to determine its prospective role in the absence of androgens in prostate cancer. %Z FOR Codes: 111201 %0 Journal Article %~ Pubmed %A Singh, Jaskirat %A Young, Lei %A Handelsman, David J %A Dong, Qihan %T Prostate epithelial expression of a novel androgen target gene. %B Journal of andrology %D 2002 %V 23 %N 5 %P 652-60 %@ 0196-3635 %X To better understand the role of androgens in prostate development and disease it is important to characterize androgen-regulated genes in the prostate. Using suppression subtractive hybridization between congenitally androgen-deficient (hpg) and androgen-replaced hpg mouse prostates, we have cloned a novel androgen up-regulated gene from mouse prostate (AUMP). The messenger RNA sequence of AUMP consists of 805 nucleotides with an open reading frame of 408 base pairs. In non-hpg mice with normal androgen levels, AUMP is selectively expressed in the prostate, as shown by reverse transcriptase-polymerase chain reaction and Northern blot analysis of 9 organs. Depletion of androgens via castration of mature mice resulted in loss of AUMP expression, whereas testosterone replacement restored it. Tissue in situ hybridization localized AUMP expression to the luminal epithelial cells of the androgen-sufficient prostate. Database searches indicate that AUMP codes for a novel protein that shares approximately 65% similarity and 35% identity to palmitoyl protein thioesterase of human, rat, mouse, and bovine. A motif for protein-transport protein, which promotes translocation as well as integration of secretory proteins into membrane, is also present. Further efforts will be made to obtain the human homologue of AUMP that will enable evaluation of its role in normal and diseased human prostate.