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https://www.readbyqxmd.com/read/27917408/prostate-specific-membrane-antigen-targeted-polymersomes-for-delivering-mocetinostat-and-docetaxel-to-prostate-cancer-cell-spheroids
#1
Fataneh Karandish, Manas K Haldar, Seungyong You, Amanda E Brooks, Benjamin D Brooks, Bin Guo, Yongki Choi, Sanku Mallik
Prostate cancer cells overexpress the prostate-specific membrane antigen (PSMA) receptors on the surface. Targeting the PSMA receptor creates a unique opportunity for drug delivery. Docetaxel is a Food and Drug Administration-approved drug for treating metastatic and androgen-independent prostate cancer, and mocetinostat is a potent inhibitor of class I histone deacetylases. In this study, we prepared reduction-sensitive polymersomes presenting folic acid on the surface and encapsulating either docetaxel or mocetinostat...
November 30, 2016: ACS Omega
https://www.readbyqxmd.com/read/27915273/altered-mirna-expression-in-high-fat-diet-induced-prostate-cancer-progression
#2
Taketoshi Nara, Shintaro Narita, Huang Mingguo, Toshiaki Yoshioka, Atsushi Koizumi, Kazuyuki Numakura, Hiroshi Tsuruta, Atsushi Maeno, Mitsuru Saito, Takamitsu Inoue, Norihiko Tsuchiya, Shigeru Satoh, Tomonori Habuchi
Recent evidence suggests that a high-fat diet (HFD) plays an important role in prostate carcinogenesis; however, underlying mechanisms largely remain unknown. Here, we investigated microRNA (miRNA) expression changes in murine prostate cancer (PCa) xenografts using two different diets: HFD and control diet. We then assessed the roles and targets of altered miRNAs in HFD-induced PCa progression. We identified 38 up- and 21 downregulated miRNAs in xenografts under HFD conditions using the miRCURY LNA™ microRNA array...
December 2016: Carcinogenesis
https://www.readbyqxmd.com/read/27913949/epigenetic-cpg-methylation-of-the-promoter-and-reactivation-of-the-expression-of-gstp1-by-astaxanthin-in-human-prostate-lncap-cells
#3
Yuqing Yang, Francisco Fuentes, Limin Shu, Chao Wang, Doug Pung, Wenji Li, Chengyue Zhang, Yue Guo, Ah-Ng Kong
Astaxanthin (AST), a red dietary carotenoid, has synergistic antioxidant effects with polyunsaturated fatty acids at low concentrations via Nuclear factor (erythroid-derived 2)-like 2 (NFE2L2 or Nrf2)/antioxidant response element (ARE) signaling. In addition, chromatin remodeling and DNA methylation-based gene silencing represent a common mechanism in prostate carcinogenesis and tumor progression from normal cells to pre-initiated cells and ultimately to invasive carcinoma. Therefore, the control of epigenetic modification and the transcriptional/translational control of the activation of Nrf2 and Nrf2-target genes, including glutathione S-transferases (GSTs), appear to be an important mechanism that protects cells against injuries from oxidative stress and cancer development...
December 2, 2016: AAPS Journal
https://www.readbyqxmd.com/read/27908170/high-resolution-digital-autoradiographic-and-dosimetric-analysis-of-heterogeneous-radioactivity-distribution-in-xenografted-prostate-tumors
#4
Oskar V Timmermand, Jenny Nilsson, Sven-Erik Strand, Jörgen Elgqvist
PURPOSE: The first main aim of this study was to illustrate the absorbed dose rate distribution from (177)Lu in sections of xenografted prostate cancer (PCa) tumors using high resolution digital autoradiography (DAR) and compare it with hypothetical identical radioactivity distributions of (90)Y or 7 MeV alpha-particles. Three dosimetry models based on either dose point kernels or Monte Carlo simulations were used and evaluated. The second and overlapping aim, was to perform DAR imaging and dosimetric analysis of the distribution of radioactivity, and hence the absorbed dose rate, in tumor sections at an early time point after injection during radioimmunotherapy using (177)Lu-h11B6, directed against the human kallikrein 2 antigen...
December 2016: Medical Physics
https://www.readbyqxmd.com/read/27905327/potential-therapeutic-effect-of-epigenetic-therapy-on-treatment-induced-neuroendocrine-prostate-cancer
#5
Xiang Xu, Yu-Hua Huang, Yan-Jing Li, Alexa Cohen, Zhen Li, Jill Squires, Wei Zhang, Xu-Feng Chen, Min Zhang, Jiao-Ti Huang
Although adenocarcinomas of the prostate are relatively indolent, some patients with advanced adenocarcinomas show recurrence of treatment-induced neuroendocrine prostate cancer, which is highly aggressive and lethal. Detailed biological features of treatment-induced neuroendocrine prostate cancer have not been characterized owing to limited biopsies/resections and the lack of a cellular model. In this study, we used a unique cellular model (LNCaP/NE1.8) to investigate the potential role of cancer stem cells in treatment-induced neuroendocrine prostate cancer with acquired resistance to hormonal therapy and chemotherapy...
November 29, 2016: Asian Journal of Andrology
https://www.readbyqxmd.com/read/27904688/molecular-mechanism-of-prostate-cancer-cell-apoptosis-induced-by-busulfan-via-adjustment-of-androgen-receptor-phosphatization
#6
Jun Liu, Guojun Jiang, Aiping Yang, Guohui Yang, Wenjuan Yang, Yi Fang
OBJECTIVE: To probe killing effect of busulfan to prostate cancer cell without androgen and the influence of androgen receptor phosphatization and analyze its molecular mechanism. METHODS: prostate cancer cell line 22RV1, LAPC4 and LNCaP treated with busulfan under androgen-free condition underwent CCK-8 examination to probe killing ability of the medicine. Flow cytometry was used to check the influence of busulfan on apoptosis rate of prostate cancer cell line LAPC4...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27896021/lithocholic-acid-induces-endoplasmic-reticulum-stress-autophagy-and-mitochondrial-dysfunction-in-human-prostate-cancer-cells
#7
Ahmed A Gafar, Hossam M Draz, Alexander A Goldberg, Mohamed A Bashandy, Sayed Bakry, Mahmoud A Khalifa, Walid AbuShair, Vladimir I Titorenko, J Thomas Sanderson
Lithocholic acid (LCA) is a secondary bile acid that is selectively toxic to human neuroblastoma, breast and prostate cancer cells, whilst sparing normal cells. We previously reported that LCA inhibited cell viability and proliferation and induced apoptosis and necrosis of androgen-dependent LNCaP and androgen-independent PC-3 human prostate cancer cells. In the present study, we investigated the roles of endoplasmic reticulum (ER) stress, autophagy and mitochondrial dysfunction in the toxicity of LCA in PC-3 and autophagy deficient, androgen-independent DU-145 cells...
2016: PeerJ
https://www.readbyqxmd.com/read/27891324/high-throughput-cell-based-compound-screen-identifies-pinosylvin-methyl-ether-and-tanshinone-iia-as-inhibitors-of-castration-resistant-prostate-cancer
#8
Kirsi Ketola, Miro Viitala, Pekka Kohonen, Vidal Fey, Zoran Culig, Olli Kallioniemi, Kristiina Iljin
Current treatment options for castration-resistant prostate cancer (CRPC) are limited. In this study, a high-throughput screen of 4910 drugs and drug-like molecules was performed to identify antiproliferative compounds in androgen ablated prostate cancer cells. The effect of compounds on cell viability was compared in androgen ablated LNCaP prostate cancer cells and in LNCaP cells grown in presence of androgens as well as in two non-malignant prostate epithelial cells (RWPE-1 and EP156T). Validation experiments of cancer specific anti-proliferative compounds indicated pinosylvin methyl ether (PSME) and tanshinone IIA as potent inhibitors of androgen ablated LNCaP cell proliferation...
March 30, 2016: Journal of Molecular Biochemistry
https://www.readbyqxmd.com/read/27889472/comprehensive-assessment-of-estrogen-receptor-beta-antibodies-in-cancer-cell-line-models-and-tissue-reveals-critical-limitations-in-reagent-specificity
#9
Adam W Nelson, Arnoud J Groen, Jodi L Miller, Anne Y Warren, Kelly A Holmes, Gerard A Tarulli, Wayne D Tilley, Benita S Katzenellenbogen, John R Hawse, Vincent J Gnanapragasam, Jason S Carroll
Estrogen Receptor-β (ERβ) has been implicated in many cancers. In prostate and breast cancer its function is controversial, but genetic studies implicate a role in cancer progression. Much of the confusion around ERβ stems from antibodies that are inadequately validated, yet have become standard tools for deciphering its role. Using an ERβ-inducible cell system we assessed commonly utilized ERβ antibodies and show that one of the most commonly used antibodies, NCL-ER-BETA, is non-specific for ERβ. Other antibodies have limited ERβ specificity or are only specific in one experimental modality...
November 23, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27877055/mir-486-5p-suppresses-prostate-cancer-metastasis-by-targeting-snail-and-regulating-epithelial-mesenchymal-transition
#10
Xiaoguang Zhang, Tong Zhang, Kuo Yang, Minghao Zhang, Keming Wang
The most common cause of death from prostate cancer (PCa) is metastases. There is an increasing body of evidence that microRNAs play an important role in the development of PCa by regulating target genes involved in tumor metastasis. Here, we identified that expression of miR-486-5p was decreased in metastatic C4-2 cells compared to non-metastatic LNCaP cells. Further validation in clinical samples showed that miR-486-5p expression was significantly decreased in metastatic PCa tissues compared to localized PCa tissues...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27862841/the-ubiquitin-ligase-ube4a-inhibits-prostate-cancer-progression-by-targeting-interleukin-like-emt-inducer-ilei
#11
Yanan Sun, Xiaopeng Jia, Qiang Gao, Xing Liu, Lianguo Hou
Epithelial to mesenchymal transition (EMT) is an important prerequisite for metastasis to secondary organs. Interleukin-like EMT inducer (ILEI) protein has been shown to translationally upregulated during EMT and metastatic progression as a consequence of aberrant TGF-β signaling. Our initial evaluation of FAM3C (encoding ILEI) and ILEI expression in normal prostate (PCS-440-010) and prostate cancer cell lines (DU145, LNCaP, and PC3) revealed detectable protein expression in only LNCaP cell line even though all cell lines tested had comparable FAM3C expression...
November 10, 2016: IUBMB Life
https://www.readbyqxmd.com/read/27862098/simvastatin-up-regulates-annexin-a10-that-can-inhibit-the-proliferation-migration-and-invasion-in-androgen-independent-human-prostate-cancer-cells
#12
Yoshiyuki Miyazawa, Yoshitaka Sekine, Haruo Kato, Yosuke Furuya, Hidekazu Koike, Kazuhiro Suzuki
BACKGROUND: Statins have recently been studied for their proapoptotic and antimetastatic effects. However, the exact mechanisms of their anticancer actions remain unclear. Using microarrays, we discovered up-regulation of annexin A10 (ANXA10) in PC-3 cells after simvastatin treatment. ANXA10 reportedly has antitumor effects. In this study, we evaluated the effects of simvastatin on ANXA10 signaling in androgen-independent prostate cancer cells. METHODS: PC-3, LNCaP-LA (which were derived from LNCaP cells and cultured in 10% charcoal-stripped fetal bovine serum for 3 months), and DU145 human prostate cancer cell lines were used...
November 8, 2016: Prostate
https://www.readbyqxmd.com/read/27861885/sensitivity-of-tp53-mutated-cancer-cells-to-the-phytoestrogen-genistein-is-associated-with-direct-inhibition-of-plk1-activity
#13
Sol-Bi Shin, Sang-Uk Woo, Young Won Chin, Young-Joo Jang, Hyungshin Yim
Polo-like kinase 1 (Plk1), a conserved Ser/Thr mitotic kinase, has been identified as a promising target for anticancer drug development because its overexpression is correlated with malignancy. Here, we found that genistein, an isoflavone, inhibits Plk1 kinase activity directly. Previously the mitotic disturbance phenomenon induced by treatment with genistein was not fully explained by its inhibitory effect on EGFR. In kinase profiling assays, it showed selectivity relative to a panel of kinases, including EGFR...
November 9, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27852261/mpc1-and-mpc2-expressions-are-associated-with-favorable-clinical-outcomes-in-prostate-cancer
#14
Xiaoli Li, Yasai Ji, Gaoyang Han, Xiaoran Li, Zhirui Fan, Yaqing Li, Yali Zhong, Jing Cao, Jing Zhao, Mingzhi Zhang, Jianguo Wen, Mariusz Adam Goscinski, Jahn M Nesland, Zhenhe Suo
BACKGROUND: Cancer cells exhibit an altered metabolism, which is characterized by a preference for aerobic glycolysis more than mitochondrial oxidation of pyruvate. Mitochondrial pyruvate carrier 1 (MPC1) and mitochondrial pyruvate carrier 2 (MPC2) play a bottleneck role by transporting pyruvate into mitochondrial through the mitochondrial inner membrane. Therefore, their protein expression in cancers may be of clinical consequences. There are studies showing low levels of MPC1 expression in colon, kidney and lung cancers, and the expression of MPC1 correlates with poor prognosis...
November 16, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27851748/chromosomal-instability-estimation-based-on-next-generation-sequencing-and-single-cell-genome-wide-copy-number-variation-analysis
#15
Stephanie B Greene, Angel E Dago, Laura J Leitz, Yipeng Wang, Jerry Lee, Shannon L Werner, Steven Gendreau, Premal Patel, Shidong Jia, Liangxuan Zhang, Eric K Tucker, Michael Malchiodi, Ryon P Graf, Ryan Dittamore, Dena Marrinucci, Mark Landers
Genomic instability is a hallmark of cancer often associated with poor patient outcome and resistance to targeted therapy. Assessment of genomic instability in bulk tumor or biopsy can be complicated due to sample availability, surrounding tissue contamination, or tumor heterogeneity. The Epic Sciences circulating tumor cell (CTC) platform utilizes a non-enrichment based approach for the detection and characterization of rare tumor cells in clinical blood samples. Genomic profiling of individual CTCs could provide a portrait of cancer heterogeneity, identify clonal and sub-clonal drivers, and monitor disease progression...
2016: PloS One
https://www.readbyqxmd.com/read/27849335/mycotoxin-verrucarin-a-inhibits-proliferation-and-induces-apoptosis-in-prostate-cancer-cells-by-inhibiting-prosurvival-akt-nf-kb-mtor-signaling
#16
Yongbo Liu, Xiaohua Gao, Dorrah Deeb, Yiguan Zhang, Jiajiu Shaw, Frederick A Valeriote, Subhash C Gautam
Trichothecenes are powerful mycotoxins that inhibit protein synthesis and induce ribotoxic stress response in mammalian cells. Verrucarin A (VC-A) is a Type D macrocyclic mycotoxin which inhibits cell proliferation and induces apoptosis in cancer cells. However, the antitumor activity of VC-A for prostate cancer cells has not been investigated. The objective of the present study was to determine the anticancer activity and its mechanism of action in hormone-responsive (LNCaP) and hormone-refractory (PC-3) carcinoma of the prostate (CaP) cell lines...
November 2016: Journal of Experimental Therapeutics & Oncology
https://www.readbyqxmd.com/read/27847991/synthesis-and-pre-clinical-evaluation-of-a-new-class-of-high-affinity-18-f-labeled-psma-ligands-for-detection-of-prostate-cancer-by-pet-imaging
#17
James Kelly, Alejandro Amor-Coarasa, Anastasia Nikolopoulou, Dohyun Kim, Clarence Williams, Shashikanth Ponnala, John W Babich
PURPOSE: Current clinical imaging of PSMA-positive prostate cancer by positron emission tomography (PET) mainly features (68)Ga-labeled tracers, notably [(68)Ga]Ga-PSMA-HBED-CC. The longer half-life of fluorine-18 offers significant advantages over Ga-68, clinically and logistically. We aimed to develop high-affinity PSMA inhibitors labeled with fluorine-18 as alternative tracers for prostate cancer. METHODS: Six triazolylphenyl ureas and their alkyne precursors were synthesized from the Glu-urea-Lys PSMA binding moiety...
November 15, 2016: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27834582/hypoxia-regulates-anxa1-expression-to-support-prostate-cancer-cell-invasion-and-aggressiveness
#18
Valentina Bizzarro, Raffaella Belvedere, Vincenzo Migliaro, Elena Romano, Luca Parente, Antonello Petrella
Annexin A1 (ANXA1) is a Ca(2+)-binding protein over-expressed in the invasive stages of prostate cancer (PCa) development; however, its role in this tumor metastatization is largely unknown. Moreover, hypoxic conditions in solid tumors have been related to poor prognosis in PCa patients. We have previously demonstrated that ANXA1 is implicated in the acquisition of chemo-resistant features in DU145 PCa cells conferring them a mesenchymal/metastatic phenotype. In this study, we have investigated the mechanisms by which ANXA1 regulates metastatic behavior in LNCaP, DU145 and PC3 cells exposed to hypoxia...
November 11, 2016: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/27833018/additive-inhibitory-effects-of-simvastatin-and-enzalutamide-on-androgen-sensitive-lncap-and-vcap-prostate-cancer-cells
#19
Heimo Syvälä, Pasi Pennanen, Merja Bläuer, Teuvo L J Tammela, Teemu J Murtola
We evaluated the effects of simvastatin and antiandrogen enzalutamide on growth and androgen signaling in androgen-sensitive LNCaP and VCaP prostate cancer cells. Simvastatin alone abolished androgen-induced growth in both cell lines but decreased androgen receptor (AR) and prostate-specific antigen protein expression only in LNCaP, indicating that statin-induced growth inhibition is beyond AR transcriptional activity in VCaP. Combination of simvastatin and enzalutamide exerted additive growth inhibition in both cell lines accompanied with strong induction of autophagy in LNCaP...
December 2, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27824899/sarcosine-up-regulates-expression-of-genes-involved-in-cell-cycle-progression-of-metastatic-models-of-prostate-cancer
#20
Zbynek Heger, Miguel Angel Merlos Rodrigo, Petr Michalek, Hana Polanska, Michal Masarik, Vitezslav Vit, Mariana Plevova, Dalibor Pacik, Tomas Eckschlager, Marie Stiborova, Vojtech Adam
The effects of sarcosine on the processes driving prostate cancer (PCa) development remain still unclear. Herein, we show that a supplementation of metastatic PCa cells (androgen independent PC-3 and androgen dependent LNCaP) with sarcosine stimulates cells proliferation in vitro. Similar stimulatory effects were observed also in PCa murine xenografts, in which sarcosine treatment induced a tumor growth and significantly reduced weight of treated mice (p < 0.05). Determination of sarcosine metabolism-related amino acids and enzymes within tumor mass revealed significantly increased glycine, serine and sarcosine concentrations after treatment accompanied with the increased amount of sarcosine dehydrogenase...
2016: PloS One
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