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Topoisomerase prostate

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https://www.readbyqxmd.com/read/29666839/the-structure-of-the-nucleus-in-normal-and-neoplastic-prostate-cells-untangling-the-role-of-type-2-dna-topoisomerases
#1
REVIEW
William G Nelson, Michael C Haffner, Srinivasan Yegnasubramanian
Donald S. Coffey, a pioneer in the study of the structural basis of mammalian genome organization, was fascinated by DNA topoisomerases, chemo-mechanical enzymes that could catalyze changes in DNA structure. Work initiated in his laboratory and carried on with his influence and inspiration has led to the elucidation of specific roles for each of the two type 2 topoisomerases in DNA replication, RNA transcription, and androgen action in prostate cells. TOP2A principally acts in DNA synthesis elongation to prevent tangling of daughter DNA molecules during genome replication and mitotic segregation; TOP2B is required for androgen-stimulation of target gene transcription...
2018: American Journal of Clinical and Experimental Urology
https://www.readbyqxmd.com/read/29519604/synthesis-and-biological-evaluation-of-histone-deacetylase-and-dna-topoisomerase-ii-targeted-inhibitors
#2
Mitsuaki Yamashita, Teruyuki Tahara, Shinya Hayakawa, Hironobu Matsumoto, Shun-Ichi Wada, Kiyoshi Tomioka, Akira Iida
HDAC inhibitors enable histones to maintain a high degree of acetylation. The resulting looser state of chromatin DNA may increase the accessibility of DNA drug targets and consequently improve the efficiency of anticancer drugs targeting DNA, such as Topo II inhibitors. A novel class of nucleoside-SAHA derivatives has been designed and synthesized based on the synergistic antitumor effects of topoisomerase II and histone deacetylase inhibitors. Their inhibitory activities toward histone deacetylases and Topo II, and their cytotoxicities in cancer cell lines, were evaluated...
February 27, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29399166/association-between-twist-and-multidrug-resistance-gene-associated-proteins-in-taxol%C3%A2-resistant-mcf-7-cells-and-a-293-cell-model-of-twist-overexpression
#3
Li Wang, Rui-Zhi Tan, Zhi-Xia Zhang, Rui Yin, Yong-Liang Zhang, Wei-Jia Cui, Tao He
Multidrug resistance (MDR) severely limits the effectiveness of chemotherapy. Previous studies have identified Twist as a key factor of acquired MDR in breast, gastric and prostate cancer. However, the underlying mechanisms of action of Twist in MDR remain unclear. In the present study, the expression levels of MDR-associated proteins, including lung resistance-related protein (LRP), topoisomerase IIα (TOPO IIα), MDR-associated protein (MRP) and P-glycoprotein (P-gp), and the expression of Twist in cancerous tissues and pericancerous tissues of human breast cancer, were examined...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29289884/4%C3%AE-amidotriazole-linked-podophyllotoxin-congeners-dna-topoisomerase-ii%C3%AE-inhibition-and-potential-anticancer-agents-for-prostate-cancer
#4
V Ganga Reddy, Srinivasa Reddy Bonam, T Srinivasa Reddy, Ravikumar Akunuri, V G M Naidu, V Lakshma Nayak, Suresh K Bhargava, H M Sampath Kumar, P Srihari, Ahmed Kamal
Topoisomerases (topo-I and topo-II) have occupied a significant role in DNA replication, transcription, and are a promising set of antitumor targets. In the present approach, a series of new 4β-amidotriazole linked podophyllotoxin derivatives (10a-i and 11a-k) were designed, synthesized by employing the click chemistry and their biological activities were evaluated. The majority of derivatives showed promising antiproliferative activity with IC50 values ranging from 1 to 10 μM on the six human cancer cell lines; cervical (HeLa), breast (MCF-7), prostate (DU-145), lung (A549), liver (HepG2) and colon (HT-29)...
January 20, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29289881/synthesis-of-podophyllotoxin-linked-%C3%AE-carboline-congeners-as-potential-anticancer-agents-and-dna-topoisomerase-ii-inhibitors
#5
Manda Sathish, Botla Kavitha, V Lakshma Nayak, Yellaiah Tangella, Ayyappan Ajitha, Shalini Nekkanti, Abdullah Alarifi, Nagula Shankaraiah, Narayana Nagesh, Ahmed Kamal
A series of new podophyllotoxin linked β-carboline congeners have been synthesized by coupling various substituted β-carboline acids with 4β-aminopodophyllotoxin. Evaluation of their anticancer activity against a panel of human cancer cell lines such as lung cancer (A549), prostate cancer (DU-145), MDA MB-231 (breast cancer), HT-29 (colon cancer) and HeLa (cervical cancer) suggested that 7i and 7j are the most cytotoxic compounds with IC50 values of 1.07 ± 0.07 μM and 1.14 ± 0.16 respectively against DU-145 cell line...
January 20, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29285240/molecular-basis-for-the-dna-damage-induction-and-anticancer-activity-of-asymmetrically-substituted-anthrapyridazone-pdz-7
#6
Majus Misiak, Mateusz Heldt, Marlena Szeligowska, Stefania Mazzini, Leonardo Scaglioni, Grzegorz J Grabe, Marcin Serocki, Jan Lica, Marta Switalska, Joanna Wietrzyk, Giovanni L Beretta, Paola Perego, Dominik Zietkowski, Maciej Baginski, Edward Borowski, Andrzej Skladanowski
Anthrapyridazones, imino analogues of anthraquinone, constitute a family of compounds with remarkable anti-cancer activity. To date, over 20 derivatives were studied, of which most displayed nanomolar cytotoxicity towards broad spectrum of cancer cells, including breast, prostate and leukemic ones. BS-154, the most potent derivative, had IC50 values close to 1 nM, however, it was toxic in animal studies. Here, we characterize another anthrapyridazone, PDZ-7, which retains high cytotoxicity while being well tolerated in mice...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29189182/design-synthesis-and-cytotoxicity-evaluation-of-new-3-5-disubstituted-2-thioxoimidazolidinones
#7
Khaled Abdellatif, Mostafa M Elbadawi, Mohammed T Elsaady, Amer Ali Abd El-Hafeez, Takashi Fujimura, Seiji Kawamoto, Ahmed I Khodair
Background Some 2-thioxoimidazolidinones have been reported as anti-prostate and anti-breast cancer agents through their inhibitory activity on topoisomerase I that is considered as a potential chemotherapeutic target. Objective A new series of 3,5-disubstituted-2-thioxoimidazolidinone derivatives 10a-f and their S-methyl analogs 11a-f were designed, synthesized and evaluated for cytotoxicity against human prostate cancer cell line (PC-3), human breast cancer cell line (MCF-7) and non-cancerous human lung fibroblast cell line (WI-38)...
November 29, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29129513/design-synthesis-and-biological-evaluation-of-new-%C3%AE-carboline-bisindole-compounds-as-dna-binding-photocleavage-agents-and-topoisomerase-i-inhibitors
#8
Jeshma Kovvuri, Burri Nagaraju, V Lakshma Nayak, Ravikumar Akunuri, M P Narasimha Rao, Ayyappan Ajitha, Narayan Nagesh, Ahmed Kamal
A series of new β-carboline-bisindole compounds were designed, synthesized and evaluated for their antiproliferative activity against human cancer cell lines, such as A549 (lung cancer), DU-145 (prostate cancer), HeLa (cervical cancer) and MCF-7 (breast cancer). All the compounds exhibited considerable antiproliferative activity. Among them, compounds 7g and 7r exhibited significant antiproliferative activity against DU-145 cells with IC50 values 1.86 and 1.80 μM respectively. Further, these compounds effectively inhibit DNA topoisomerase I activity and can also cleave the pBR322 plasmid upon irradiation with UV light...
January 1, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29107586/ru-fe-bimetallic-complexes-synthesis-characterization-cytotoxicity-and-study-of-their-interactions-with-dna-hsa-and-human-topoisomerase-ib
#9
Jessica E Takarada, Adriana P M Guedes, Rodrigo S Correa, Elisângela de P Silveira-Lacerda, Silvia Castelli, Federico Iacovelli, Victor Marcelo Deflon, Alzir Azevedo Batista, Alessandro Desideri
Three ruthenium/iron-based compounds, 1: [Ru(MIm)(bipy)(dppf)]PF6 (MIm = 2-mercapto-1-methylimidazole anion), 2: [RuCl(Im)(bipy)(dppf)]PF6 (Im = imidazole), and 3: [Ru(tzdt)(bipy)(dppf)]PF6 (tzdt = 1,3-thiazolidine-2-thione anion) (dppf = 1,1'-bis(diphenylphosphine)ferrocene and bipy = 2,2'-bipyridine), were synthesized, and characterized by elemental analyses, conductivity, UV/Vis, IR,1 H,13 C and31 P{1H} NMR spectroscopies, and by electrochemical technique. The complex 3 was also characterized by single-crystal X-ray...
December 15, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29105933/sarcosine-influences-apoptosis-and-growth-of-prostate-cells-via-cell-type-specific-regulation-of-distinct-sets-of-genes
#10
Miguel A Merlos Rodrigo, Vladislav Strmiska, Eva Horackova, Hana Buchtelova, Petr Michalek, Marie Stiborova, Tomas Eckschlager, Vojtech Adam, Zbynek Heger
BACKGROUND: Sarcosine is a widely discussed oncometabolite of prostate cells. Although several reports described connections between sarcosine and various phenotypic changes of prostate cancer (PCa) cells, there is still a lack of insights on the complex phenomena of its effects on gene expression patterns, particularly in non-malignant and non-metastatic cells. METHODS: To shed more light on this phenomenon, we performed parallel microarray profiling of RNA isolated from non-malignant (PNT1A), malignant (22Rv1), and metastatic (PC-3) prostate cell lines treated with sarcosine...
November 6, 2017: Prostate
https://www.readbyqxmd.com/read/29048618/dual-action-of-nsc606985-on-cell-growth-and-apoptosis-mediated-through-pkc%C3%AE-in-prostatic-cancer-cells
#11
Xin Wang, Chen Tan, Guo Wang, Jing-Jing Cai, Li-Ping Wang, Julianne Imperato-McGinley, Yuan-Shan Zhu
Chemotherapy is a vital therapeutic strategy for castration-resistant prostate cancer (CRPC). We have previously shown that NSC606985 (NSC), a camptothecin (CPT) analog, induced cell apoptosis via interacting with topoisomerase I (Topo I) in prostate cancer cells. In the present study, the effect and mechanism of CPT analogs in LAPC4 cells were investigated. LAPC-4 cells were treated with NSC, CPT, and topotecan. Cell proliferation, apoptosis, and protein kinase Cδ (PKCδ) subcellular activation were measured at different doses and time-points, with or without PKCδ inhibition or knockdown of PKCδ expression...
November 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29031818/camptothecin-and-its-analog-sn-38-the-active-metabolite-of-irinotecan-inhibit-binding-of-the-transcriptional-regulator-and-oncoprotein-fubp1-to-its-dna-target-sequence-fuse
#12
Sabrina Khageh Hosseini, Stefanie Kolterer, Marlene Steiner, Viktoria von Manstein, Katharina Gerlach, Jörg Trojan, Oliver Waidmann, Stefan Zeuzem, Jörg O Schulze, Steffen Hahn, Dieter Steinhilber, Volker Gatterdam, Robert Tampé, Ricardo M Biondi, Ewgenij Proschak, Martin Zörnig
The transcriptional regulator FUSE Binding Protein 1 (FUBP1) is overexpressed in more than 80% of all human hepatocellular carcinomas (HCCs) and other solid tumor entities including prostate and colorectal carcinoma. FUBP1 expression is required for HCC tumor cell expansion, and it functions as an important pro-proliferative and anti-apoptotic oncoprotein that binds to the single-stranded DNA sequence FUSE to regulate the transcription of a variety of target genes. In this study, we screened an FDA-approved drug library and discovered that the Topoisomerase I (TOP1) inhibitor camptothecin (CPT) and its derivative 7-ethyl-10-hydroxycamptothecin (SN-38), the active irinotecan metabolite that is used in the clinics in combination with other chemotherapeutics to treat carcinoma, inhibit FUBP1 activity...
December 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28840551/role-of-protein-linked-dna-breaks-in-cancer
#13
Walaa R Allam, Mohamed E Ashour, Amr A Waly, Sherif El-Khamisy
Topoisomerases are a group of specialized enzymes that function to maintain DNA topology by introducing transient DNA breaks during transcription and replication. As a result of abortive topoisomerases activity, topoisomerases catalytic intermediates may be trapped on the DNA forming topoisomerase cleavage complexes (Topcc). Topoisomerases trapping on the DNA is the mode of action of several anticancer drugs, it lead to formation of protein linked DAN breaks (PDBs). PDBs are now considered as one of the most dangerous forms of endogenous DNA damage and a major threat to genomic stability...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28753517/design-synthesis-and-antiproliferative-activity-of-decarbonyl-luotonin-analogues
#14
Abdulrahman I Almansour, Natarajan Arumugam, Raju Suresh Kumar, S M Mahalingam, Samaresh Sau, Giulia Bianchini, J Carlos Menéndez, Mohammad Altaf, Hazem A Ghabbour
A small library of benzimidazole-fused pyrrolo[3,4-b]quinoline has been synthesized from readily available benzimidazole 2-carbaldehyde and various substituted arylamines in good to excellent yields utilizing an intramolecular Povarov reaction catalyzed by boron trifluoride diethyl etharate as the key final step. The compounds thus synthesized can be considered as decarbonyl analogues of the anticancer alkaloid luotonin A and were evaluated in a DNA relaxation assay for their ability to inhibit human topoisomerase I...
September 29, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28368209/enhanced-cytotoxic-effect-of-camptothecin-nanosponges-in-anaplastic-thyroid-cancer-cells-in-vitro-and-in-vivo-on-orthotopic-xenograft-tumors
#15
Casimiro Luca Gigliotti, Benedetta Ferrara, Sergio Occhipinti, Elena Boggio, Giuseppina Barrera, Stefania Pizzimenti, Mirella Giovarelli, Roberto Fantozzi, Annalisa Chiocchetti, Monica Argenziano, Nausicaa Clemente, Francesco Trotta, Caterina Marchiò, Laura Annaratone, Renzo Boldorini, Umberto Dianzani, Roberta Cavalli, Chiara Dianzani
Anaplastic carcinoma of the thyroid (ATC) is a lethal human malignant cancer with median survival of 6 months. To date, no treatment has substantially changed its course, which makes urgent need for the development of novel drugs or novel formulations for drug delivery. Nanomedicine has enormous potential to improve the accuracy of cancer therapy by enhancing availability and stability, decreasing effective doses and reducing side effects of drugs. Camptothecin (CPT) is an inhibitor of DNA topoisomerase-I with several anticancer properties but has poor solubility and a high degradation rate...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/27771897/profiling-of-signaling-proteins-in-penumbra-after-focal-photothrombotic-infarct-in-the-rat-brain-cortex
#16
Svetlana Demyanenko, Anatoly Uzdensky
In ischemic stroke, cell damage propagates from infarct core to surrounding tissue. To reveal proteins involved in neurodegeneration and neuroprotection, we explored the protein profile in penumbra surrounding the photothrombotic infarct core induced in rat cerebral cortex by local laser irradiation after Bengal Rose administration. Using antibody microarrays, we studied changes in expression of 224 signaling proteins 1, 4, or 24 h after photothrombotic infarct compared with untreated contralateral cortex...
October 22, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27643560/novel-2-aryl-4-4-hydroxyphenyl-5h-indeno-1-2-b-pyridines-as-potent-dna-non-intercalative-topoisomerase-catalytic-inhibitors
#17
Seojeong Park, Tara Man Kadayat, Kyu-Yeon Jun, Til Bahadur Thapa Magar, Ganesh Bist, Aarajana Shrestha, Eung-Seok Lee, Youngjoo Kwon
On the basis of previous reports on the importance of thienyl, furyl or phenol group substitution on 5H-indeno[1,2-b]pyridine skeleton, a new series of rigid 2-aryl-4-(4'-hydroxyphenyl)-5H-indeno[1,2-b]pyridine derivatives were systematically designed and synthesized. Topoisomerase inhibitory activity and antiproliferative activity of all the synthesized compounds were determined using human colorectal (HCT15), breast (T47D), prostate (DU145) and cervix (HeLa) cancer cells. Compounds 9, 10, 12, 13, 15, 16, 18 and 19 with thienyl or furyl moiety at the 2-position and hydroxyl group at the meta or para positions of 4-phenyl ring displayed strong to moderate topoisomerase IIα (topo IIα) inhibitory activity and significant antiproliferative activity...
January 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27537875/the-role-of-%C3%AE-1-adrenoceptor-antagonists-in-the-treatment-of-prostate-and-other-cancers
#18
REVIEW
Mallory Batty, Rachel Pugh, Ilampirai Rathinam, Joshua Simmonds, Edwin Walker, Amanda Forbes, Shailendra Anoopkumar-Dukie, Catherine M McDermott, Briohny Spencer, David Christie, Russ Chess-Williams
This review evaluates the role of α-adrenoceptor antagonists as a potential treatment of prostate cancer (PCa). Cochrane, Google Scholar and Pubmed were accessed to retrieve sixty-two articles for analysis. In vitro studies demonstrate that doxazosin, prazosin and terazosin (quinazoline α-antagonists) induce apoptosis, decrease cell growth, and proliferation in PC-3, LNCaP and DU-145 cell lines. Similarly, the piperazine based naftopidil induced cell cycle arrest and death in LNCaP-E9 cell lines. In contrast, sulphonamide based tamsulosin did not exhibit these effects...
August 16, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27435006/new-spiro-acridines-dna-interaction-antiproliferative-activity-and-inhibition-of-human-dna-topoisomerases
#19
Sinara Mônica Vitalino de Almeida, Elizabeth Almeida Lafayette, Willams Leal Silva, Vanessa de Lima Serafim, Thais Meira Menezes, Jorge Luiz Neves, Ana Lucia Tasca Gois Ruiz, João Ernesto de Carvalho, Ricardo Olímpio de Moura, Eduardo Isidoro Carneiro Beltrão, Luiz Bezerra de Carvalho Júnior, Maria do Carmo Alves de Lima
Two new spiro-acridines were synthesized by introducing cyano-N-acylhydrazone between the acridine and phenyl rings followed by spontaneous cyclization. The final compounds (E)-1'-(benzylideneamino)-5'-oxo-1',5'-dihydro-10H-spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-01) and (E)-1'-((4-methoxybenzylidene)amino)-5'-oxo-1',5'-dihydro-10H-spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-02) were evaluated for their interactions with calf thymus DNA, antiproliferative and human topoisomerase I and IIα inhibitory activities...
November 2016: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27301177/in-vitro-and-in-vivo-therapeutic-evaluation-of-camptothecin-encapsulated-%C3%AE-cyclodextrin-nanosponges-in-prostate-cancer
#20
Casimiro Luca Gigliotti, Rosalba Minelli, Roberta Cavalli, Sergio Occhipinti, Giuseppina Barrera, Stefania Pizzimenti, Giuseppe Cappellano, Elena Boggio, Laura Conti, Roberto Fantozzi, Mirella Giovarelli, Francesco Trotta, Umberto Dianzani, Chiara Dianzani
Camptothecin (CPT), a pentacyclic alkaloid, is an inhibitor of DNA Topoisomerase-I and shows a wide spectrum of anti-cancer activities. The use of CPT has been hampered by poor aqueous solubility and a high degradation rate. Previously, it has been reported that CPT encapsulated in β-cyclodextrin-nanosponges (CN-CPT) overcomes these disadvantages and improves the CPT's inhibitory effect on DU145 prostate tumor cell lines, and PC-3 growth in vitro. This work extends these observations by showing that CN-CPT significantly inhibits the adhesion and migration of these tumor cells and their STAT3 phosphorylation...
January 2016: Journal of Biomedical Nanotechnology
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