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https://www.readbyqxmd.com/read/28802253/the-combination-of-metformin-and-valproic-acid-induces-synergistic-apoptosis-in-the-presence-of-p53-and-androgen-signaling-in-prostate-cancer
#1
Linh N K Tran, Ganessan Kichenadasse, Lisa M Butler, Margaret M Centenera, Katherine L Morel, Rebecca J Ormsby, Michael Z Michael, Karen M Lower, Pamela J Sykes
We investigated the potential of combining the hypoglycemic drug metformin (MET) and the anti-epileptic drug valproic acid (VPA), which act via different biochemical pathways, to provide enhanced anti-tumor responses in prostate cancer. Prostate cancer cell lines (LNCaP and PC-3), normal prostate epithelial cells (PrEC), and patient-derived prostate tumor explants were treated with MET and/or VPA. Proliferation and apoptosis were assessed. The role of p53 in response to MET+VPA was assessed in cell lines using RNA interference in LNCaP (p53(+)) and ectopic expression of p53 in PC-3 (p53(-))...
August 11, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28798482/retinoblastoma-protein-rb-links-hypoxia-to-altered-mechanical-properties-in-cancer-cells-as-measured-by-an-optical-tweezer
#2
S Khakshour, M P Labrecque, H Esmaeilsabzali, F J S Lee, M E Cox, E J Park, T V Beischlag
Hypoxia modulates actin organization via multiple pathways. Analyzing the effect of hypoxia on the biophysical properties of cancer cells is beneficial for studying modulatory signalling pathways by quantifying cytoskeleton rearrangements. We have characterized the biophysical properties of human LNCaP prostate cancer cells that occur in response to loss of the retinoblastoma protein (Rb) under hypoxic stress using an oscillating optical tweezer. Hypoxia and Rb-loss increased cell stiffness in a fashion that was dependent on activation of the extracellular signal-regulated kinase (ERK) and the protein kinase B (AKT)- mammalian target of rapamycin (MTOR) pathways...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28797006/amiloride-is-effective-in-the-management-of-abiraterone-induced-mineralocorticoid-excess-syndrome-without-interfering-with-its-antineoplastic-activity
#3
Francesca Bedussi, Diego Galli, Martina Fragni, Francesca Valcamonico, Elisa Rossini, Alberto Dalla Volta, Sara Vezzoli, Elisa Roca, Vittorio Ferrari, Barbara Lazzari, Maurizio Memo, Sandra Sigala, Alfredo Berruti
BACKGROUND: The administration of abiraterone acetate (abiraterone) leads to an adrenocorticotropic hormone (ACTH)-driven increase in mineralocorticoid hormones, requiring glucocorticoid supplementation that may stimulate the growth of prostate cancer (PCa). Amiloride is a drug that selectively reduces the aldosterone-sensitive Na+/K+ exchange and could be effective in the management of mineralocorticoid excess syndrome (MCES). METHODS: The efficacy of amiloride + hydrochlorothiazide (HCT) in the clinical management of abiraterone-induced MCES was assessed in 5 consecutive patients with castration-resistant PCa (CRPC)...
August 11, 2017: Pharmacology
https://www.readbyqxmd.com/read/28795782/variation-on-composition-and-bioactivity-of-essential-oils-of-four-common-curcuma-herbs
#4
Lanyue Zhang, Zhiwen Yang, Dingkang Chen, Zebin Huang, Yongliang Li, Xinzi Lan, Ping Su, Wanyi Pan, Wei Zhou, Xi Zheng, Zhiyun Du
Chemical compositions, antioxidative, antimicrobial, anti-inflammatory and cytotoxic activities of essential oils extracted from four common Curcuma species (Curcuma longa, Curcuma phaeocaulis, Curcuma wenyujin and Curcuma kwangsiensis) rhizomes in China are comparatively studied. In total, 47, 49, 35 and 30 compounds are identified in C. longa, C. phaeocaulis, C. wenyujin and C. kwangsiensis essential oils by GC-MS, and their richest compounds are ar-turmerone (21.67%), elemenone (19.41%), curdione (40.23%) and (36...
August 10, 2017: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/28794625/paclitaxel-loaded-and-a10-3-2-aptamer-targeted-poly-lactide-co-glycolic-acid-nanobubbles-for-ultrasound-imaging-and-therapy-of-prostate-cancer
#5
Meng Wu, Ying Wang, Yiru Wang, Mingbo Zhang, Yukun Luo, Jie Tang, Zhigang Wang, Dong Wang, Lan Hao, Zhibiao Wang
In the current study, we synthesized prostate cancer-targeting poly(lactide-co-glycolic acid) (PLGA) nanobubbles (NBs) modified using A10-3.2 aptamers targeted to prostate-specific membrane antigen (PSMA) and encapsulated paclitaxel (PTX). We also investigated their impact on ultrasound (US) imaging and therapy of prostate cancer. PTX-A10-3.2-PLGA NBs were developed using water-in-oil-in-water (water/oil/water) double emulsion and carbodiimide chemistry approaches. Fluorescence imaging together with flow cytometry verified that the PTX-A10-3...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28782625/shifted-golgi-targeting-of-glycosyltransferases-and-%C3%AE-mannosidase-ia-from-giantin-to-gm130-grasp65-results-in-formation-of-high-mannose-n-glycans-in-aggressive-prostate-cancer-cells
#6
Ganapati Bhat, Vishwanath-Reddy Hothpet, Ming-Fong Lin, Pi-Wan Cheng
BACKGROUND: There is a pressing need for biomarkers that can distinguish indolent from aggressive prostate cancer to prevent over-treatment of patients with indolent tumor. METHODS: Golgi targeting of glycosyltransferases was characterized by confocal microscopy after knockdown of GM130, giantin, or both. N-glycans on a trans-Golgi enzyme β4galactosyltransferase-1 isolated by immunoprecipitation from androgen-sensitive and independent prostate cancer cells were determined by matrix-assisted laser desorption-time of flight-mass spectrometry...
August 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28774496/adrenal-c11-oxy-c21-steroids-contribute-to-the-c11-oxy-c19-steroid-pool-via-the-backdoor-pathway-in-the-biosynthesis-and-metabolism-of-21-deoxycortisol-and-21-deoxycortisone
#7
Lise Barnard, Rachelle Gent, Desmaré van Rooyen, Amanda C Swart
21-Hydroxylase deficiency presents with increased levels of cytochrome P450 21-hydroxylase substrates, progesterone and 17α-hydroxyprogesterone, which have been implicated in the production of androgens via the backdoor pathway. This study shows the biosynthesis of C11-oxy C21 steroids, 21-deoxycortisol and 21-deoxycortisone, and their metabolism by steroidogenic enzymes in the backdoor pathway yielding novel steroid metabolites: 5α-pregnan-11β,17α-diol-3,20-dione; 5α-pregnan-17α-ol-3,11,20-trione; 5α-pregnan-3α,11β,17α-triol-20-one and 5α-pregnan-3α,17α-diol-11,20-dione...
July 31, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28771887/acsl3-promotes-intratumoral-steroidogenesis-in-prostate-cancer-cells
#8
Toshiro Migita, Ken-Ichi Takayama, Tomohiko Urano, Daisuke Obinata, Kazutaka Ikeda, Tomoyoshi Soga, Satoru Takahashi, Satoshi Inoue
Long-chain acyl-coenzyme A (CoA) synthetase 3 (ACSL3) is an androgen-responsive gene involved in the generation of fatty acyl-CoA esters. ACSL3 is expressed in both androgen-sensitive and castration-resistant prostate cancer (CRPC). However, its role in prostate cancer remains elusive. We overexpressed ACSL3 in androgen-dependent LNCaP cells and examined the downstream effectors of ACSL3. Furthermore, we examined the role of ACSL3 in the androgen metabolism of prostate cancer. ACSL3 overexpression led to upregulation of several genes such as aldo-keto reductase 1C3 (AKR1C3) involved in steroidogenesis, which utilizes adrenal androgen dehydroepiandrosterone sulfate (DHEAS) as substrate, and downregulated androgen-inactivating enzyme UDP-glucuronosyltransferase 2 (UGT2B)...
August 3, 2017: Cancer Science
https://www.readbyqxmd.com/read/28768769/leucine-rich-repeat-containing-g-protein-coupled-receptor-4-lgr4-is-necessary-for-prostate-cancer-metastasis-via-epithelial-mesenchymal-transition
#9
Weijia Luo, Peng Tan, Melissa Rodriguez, Lian He, Kunrong Tan, Li Zeng, Stefan Siwko, Mingyao Liu
Prostate cancer is a highly penetrant disease among men in industrialized societies, yet the factors regulating the transition from indolent to aggressive and metastatic cancer remain poorly understood. We found that men with prostate cancers expressing high levels of the G protein-coupled receptor LGR4 had a significantly shorter recurrence-free survival compared to patients with cancers having low LGR4 expression. LGR4 expression was elevated in human prostate cancer cell lines with metastatic potential. We therefore generated a novel transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model to investigate the role of Lgr4 in prostate cancer development and metastasis in vivo...
August 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28760528/3-o-substituted-3-4-5-trimethoxyflavonols-synthesis-and-cell-based-evaluation-as-anti-prostate-cancer-agents
#10
Xiang Li, Maizie Lee, Guanglin Chen, Qiang Zhang, Shilong Zheng, Guangdi Wang, Qiao-Hong Chen
Twenty-two 3-O-substituted-3',4',5'-trimethoxyflavonols have been designed and synthesized for their anti-proliferative activity towards three human prostate cancer cell lines. Our results indicate that most of them are significantly more potent than the parent 3',4',5'-trimethoxyflavonol in inhibiting the cell proliferation in PC-3 and LNCaP prostate cancer cell models. 3-O-Substituted-3',4',5'-trimethoxyflavonols have generally higher potency towards PC-3 and LNCaP cell lines than the DU145 cell line. Incorporation of an ethyl group to 3-OH of 3',4',5'-trimethoxyflavonol leads to 3-O-ethyl-3',4',5'-trimethoxyflavonol as the optimal derivative with up to 36-fold enhanced potency as compared with the corresponding lead compound 3',4',5'-trimethoxyflavonol, but with reversed PC-3 cell apoptotic response...
July 21, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28758913/versatility-of-pyridoxal-phosphate-as-a-coating-of-iron-oxide-nanoparticles
#11
Debora Bonvin, Ulrich J Aschauer, Jessica A M Bastiaansen, Matthias Stuber, Heinrich Hofmann, Marijana Mionić Ebersold
Pyridoxal 5'-phosphate (PLP) is the most important cofactor of vitamin B₆-dependent enzymes, which catalyses a wide range of essential body functions (e.g., metabolism) that could be exploited to specifically target highly metabolic cells, such as tumour metastatic cells. However, the use of PLP as a simultaneous coating and targeting molecule, which at once provides colloidal stability and specific biological effects has not been exploited so far. Therefore, in this work iron oxide nanoparticles (IONPs) were coated by PLP at two different pH values to tune PLP bonding (e...
July 29, 2017: Nanomaterials
https://www.readbyqxmd.com/read/28757136/iminoenamine-based-novel-androgen-receptor-antagonist-exhibited-anti-prostate-cancer-activity-in-androgen-independent-prostate-cancer-cells-through-inhibition-of-akt-pathway
#12
S Divakar, K Saravanan, P Karthikeyan, R Elancheran, S Kabilan, K K Balasubramanian, Rajlakshmi Devi, J Kotoky, M Ramanathan
Treatment by androgen receptor (AR) antagonists is one of the regimens for prostate cancer. The prolonged treatment with AR antagonist leads to the expression of point mutation in the ligand binding domain of the AR. This point mutation causes resistance to AR antagonist by converting them into an agonist. The T887A mutated AR was frequently expressed in androgen independent prostate cancer (AIPC) patients. Through literature survey and molecular modelling, we have identified a novel AR antagonist having a bulky β-iminoenamine BF2 complex scaffold...
July 27, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28757062/design-synthesis-and-biological-evaluation-of-novel-3-oxo-4-oxa-5%C3%AE-androst-17%C3%AE-amide-derivatives-as-dual-5%C3%AE-reductase-inhibitors-and-androgen-receptor-antagonists
#13
Kejing Lao, Jie Sun, Chong Wang, Ying Wang, Qidong You, Hong Xiao, Hua Xiang
Prostate cancer (PCa) is the second leading cause of death in men. Recently, some researches have showed that 5α-reductase inhibitors were beneficial in PCa treatment as well. In this study, a series of novel 3-oxo-4-oxa-5α-androst-17β-amide derivatives have been designed and synthesized in a more simple and convenient method. Most of the synthesized compounds displayed good 5α-reductase inhibitory activities and androgen receptor binding affinities. Their anti-proliferation activities in PC-3 and LNCaP cell lines were also evaluated and the results indicated that most of the synthesized compounds exhibited potent anti-proliferative activities...
May 27, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28756013/5-or-and-20-o-alkyl-2-3-dehydrosilybins-synthesis-and-biological-profiles-on-prostate-cancer-cell-models
#14
Bao Vue, Xiaojie Zhang, Timmy Lee, Nandini Nair, Sheng Zhang, Guanglin Chen, Qiang Zhang, Shilong Zheng, Guangdi Wang, Qiao-Hong Chen
To investigate the effects of alkylation at 5-OH and 20-OH of 2,3-dehydrosilybin on prostate cancer cell proliferation, the synthetic approaches to 5- or/and 20-O-alkyl-2,3-dehydrosilybins, through a multi-step sequence from commercially available silybin, have been successfully developed. The first three reactions in the syntheses were completed through a one-pot procedure by managing anaerobic and aerobic conditions. With these synthetic methods in hand, twenty-one 2,3-dehydrosilybins, including seven 20-O-alkyl, seven 5,20-O-dialkyl, and seven 5-O-alkyl-2,3-dehydrosilybins, have been achieved for the evaluation of their biological profiles...
July 20, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28753573/implications-of-pi3k-akt-inhibition-on-rest-protein-stability-and-neuroendocrine-phenotype-acquisition-in-prostate-cancer-cells
#15
Ruiqui Chen, Yinan Li, Ralph Buttyan, Xuesen Dong
Treatment-induced neuroendocrine prostate cancer (t-NEPC) is an aggressive subtype of prostate cancer (PCa) that arises as a consequence of rigorous androgen receptor (AR) pathway inhibition (ARPI) therapies. While the PI3K/AKT pathway has been investigated as a co-therapeutic target with ARPI for advanced PCa, whether this strategy can prevent tumor progression to t-NEPC remains unknown. Here, we report that PI3K/AKT inhibition alone reduces RE-1 silencing transcription factor (REST) protein expression and induces multiple NE markers in PCa cells...
July 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28753517/design-synthesis-and-antiproliferative-activity-of-decarbonyl-luotonin-analogues
#16
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...
July 18, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28752972/-the-inhibitory-effect-and-mechanism-of-human-umbilical-cord-mesenchymal-stem-cells-on-prostate-cancer-metastasis
#17
Yun-Jian Wu, Qiang Wei, Ming Nie, Yong Yin, Yong Xi
OBJECTIVE: To test whether umbilical cord mesenchymal stem cells (UMSCs) can inhibit the growth and metastasis of prostate cancer cells, and to investigate the mechanism. METHODS: The UMSCs from human umbilical cord tissue were isolate by explant technique. After being co-cultured the UMSCs with LNCaP and PC-3 cells for 24 h, 48 h and 72 h, LNCaP and PC-3 cells' proliferation were tested and the 72 h proliferation inhibitory rate (IR) was calculated. Transwell invasion assay was used to test the migration and invasion abilities of prostate cancer cells after being co-cultured with UMSCs for 48 h...
July 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28749250/discovery-of-thalicthuberine-as-a-novel-antimitotic-agent-from-nature-that-disrupts-microtubule-dynamics-and-induces-apoptosis-in-prostate-cancer-cells
#18
Claire Levrier, Anja Rockstroh, Brian Gabrielli, Maria Kavallaris, Melanie Lehman, Rohan A Davis, Martin C Sadowski, Colleen C Nelson
We report for the first time the mechanism of action of the natural product thalicthuberine (TH) in prostate and cervical cancer cells. TH induced a strong accumulation of LNCaP cells in mitosis, severe mitotic spindle defects and asymmetric cell divisions, ultimately leading to mitotic catastrophe accompanied by cell death through apoptosis. However, unlike microtubule-binding drugs (vinblastine and paclitaxel), TH did not directly inhibit tubulin polymerization when tested in a cell-free system, whereas it reduced cellular microtubule polymer mass in LNCaP cells...
July 27, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28746210/anticancer-effect-of-saussurea-lappa-extract-via-dual-control-of-apoptosis-and-autophagy-in-prostate-cancer-cells
#19
Xue Tian, Hae Seong Song, Young Mi Cho, Bongkyun Park, Yoon-Jae Song, Sunphil Jang, Se Chan Kang
To demonstrate the mechanisms of the curative effect of Saussurea lappa ethanol extract (SLE) against prostate cancer, we evaluated the effect of SLE on the induction of apoptosis and autophagy and investigated whether SLE-induced autophagy exerts a pro-survival or pro-apoptotic effect in lymph node carcinoma of the prostate (LNCaP) prostate cancer cells. SLE was prepared using 100% ethanol and added to LNCaP cells for 24 hours. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and cell apoptosis was evaluated by Tali assay...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28746182/plumbagin-loaded-aptamer-targeted-poly-d-l-lactic-co-glycolic-acid-b-polyethylene-glycol-nanoparticles-for-prostate-cancer-therapy
#20
Minjie Pan, Weifeng Li, Jun Yang, Zhiqin Li, Jun Zhao, Yajun Xiao, Yifei Xing, Xiaoping Zhang, Wen Ju
Plumbagin inhibits the growth, metastasis, and invasion of prostate cancer (PCa). However, its lower bioavailability limits biopharmaceutical properties due to insolubility in water. Prostate-specific membrane antigen (PSMA) aptamer-targeted nanoparticles (NPs) significantly enhanced cytotoxicity in prostate epithelial cells. This study aimed to investigate the effects of plumbagin-loaded prostate-specific membrane antigen (PSMA) aptamer-targeted poly D,L-lactic-co-glycolic acid-b-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) on prostate cancer (PCa) in vitro...
July 2017: Medicine (Baltimore)
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