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Z Kozovska, A Patsalias, V Bajzik, E Durinikova, L Demkova, S Jargasova, B Smolkova, J Plava, L Kucerova, M Matuskova
BACKGROUND: Recent evidence in cancer research, developed the notion that malignant tumors consist of different subpopulations of cells, one of them, known as cancer stem cells, being attributed many important properties such as enhanced tumorigenicity, proliferation potential and profound multidrug resistance to chemotherapy. Several key stem cells markers were identified in colon cancer. In our study we focused on the aldehyde dehydrogenase type 1 (ALDH1) expression in colon cancer-derived cell lines HT-29/eGFP, HCT-116/eGFP and LS-180/eGFP, and its role in the chemoresistance and tumorigenic potential...
June 15, 2018: BMC Cancer
Jeff Hirst, Harsh B Pathak, Stephen Hyter, Ziyan Y Pessetto, Thuc Ly, Stefan Graw, Devin C Koestler, Adam J Krieg, Katherine F Roby, Andrew K Godwin
Drug development for front-line treatment of epithelial ovarian cancer (EOC) has been stagnant for almost three decades. Traditional cell culture methods for primary drug screening do not always accurately reflect clinical disease. To overcome this barrier, we grew a panel of EOC cell lines in three-dimensional (3D) cell cultures to form multicellular tumor spheroids (MCTS). We characterized these MCTS for molecular and cellular features of EOC and performed a comparative screen with cells grown using two-dimensional (2D) cell culture to identify previously unappreciated anti-cancer drugs...
June 11, 2018: Cancer Research
Hui Li, Ying Wang, Jiali Yang, Xiaoming Liu, Juan Shi
BACKGROUND: The incidence of lung cancer is gradually increased, and the cystic fibrosis transmembrane conductance regulator (CFTR) has recently demonstrated to have an implication in the deoncogenesis and malignant transformation of many types of cancers. The aim of this study is to investigate impacts of CFTR on the malignant features of lung adenocarcinoma A549 cells. METHODS: The capacity of cell proliferation, migration, invasion and clonogenicity of non-small cell lung cancer A549 cells were detected by CCK8 cell proliferation assay, cell scratch assay, Transwell cell invasion assay and clone formation assay, respectively...
February 20, 2018: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
Yan Chen, Jin-Yi Zhu, Kwon Ho Hong, David C Mikles, Gunda I Georg, Alex S Goldstein, John K Amory, Ernst Schönbrunn
Enzymes of the ALDH1A subfamily of aldehyde dehydrogenases are crucial in regulating retinoic acid (RA) signaling and have received attention as potential drug targets. ALDH1A2 is the primary RA-synthesizing enzyme in mammalian spermatogenesis and is therefore considered a viable drug target for male contraceptive development. However, only a small number of ALDH1A2 inhibitors have been reported, and information on the structure of ALDH1A2 was limited to the NAD-liganded enzyme void of substrate or inhibitors...
March 16, 2018: ACS Chemical Biology
Xingxing Xu, Chuanyin Li, Xiaobo Gao, Kun Xia, Hui Guo, Yali Li, Zijian Hao, Lei Zhang, Daming Gao, Chenfan Xu, Huatai Xu, Zhi-Qi Xiong, Zilong Qiu, Ling Mei, Xiaoduo Xie, Kangcheng Ruan, Ronggui Hu
The autism spectrum disorders (ASDs) are a collection of human neurological disorders with heterogeneous etiologies. Hyperactivity of E3 ubiquitin (Ub) ligase UBE3A, stemming from 15q11-q13 copy number variations, accounts for 1%-3% of ASD cases worldwide, but the underlying mechanisms remain incompletely characterized. Here we report that the functionality of ALDH1A2, the rate-limiting enzyme of retinoic acid (RA) synthesis, is negatively regulated by UBE3A in a ubiquitylation-dependent manner. Excessive UBE3A dosage was found to impair RA-mediated neuronal homeostatic synaptic plasticity...
January 2018: Cell Research
Michael Haenisch, Piper M Treuting, Thea Brabb, Alex S Goldstein, Kathryn Berkseth, John K Amory, Jisun Paik
BACKGROUND: Retinoic acid (RA) is known to play a role in weight regulation. Because mice without ALDH1A1, a major RA synthesizing enzyme, are resistant to diet-induced obesity, we tested a hypothesis that pharmacological inhibition of RA synthesis can suppress weight gain in a murine model of diet-induced obesity. METHODS: C57BL/6J male mice were fed a high fat diet (HFD) for 8 weeks to induce obesity and then randomized to a HFD with or without WIN 18,446, an RA synthesis inhibitor, for an additional 9 weeks...
January 2018: Obesity Research & Clinical Practice
Juan Carlos Gallardo-Pérez, Alhelí Adán-Ladrón de Guevara, Alvaro Marín-Hernández, Rafael Moreno-Sánchez, Sara Rodríguez-Enríquez
Cancer stem cells are responsible for tumor recurrence and metastasis. A new highly reproducible procedure for human breast cancer MCF-7 stem cells (BCSC) isolation and selection was developed by using a combination of hypoxia/hypoglycemia plus taxol and adriamycin for 24h. The BCSC enriched fraction (i) expressed (2-15 times) the typical stemness protein markers CD44+, ALDH1A3 and Oct 3/4; (ii) increased its clonogenicity index (20-times), invasiveness profile (>70%), migration capacity (100%) and ability to form mammospheres, compared to its non-metastatic MCF-7 counterpart...
October 2017: Biochimica et Biophysica Acta
Serkan Senol, Abdullah Aydin, Duygu Kosemetin, Dilek Ece, Ibrahim Akalin, Hasan Abuoglu, Esra Akdeniz Duran, Dincer Aydin, Burcak Erkol
Expression levels of several molecules implicated in carcinogenesis were examined by immunohistochemical staining, and the prognostic significance of their expression levels in gastric adenocarcinoma (GA) was evaluated. A total of 115 GA and 20 control gastric tissue samples were evaluated by immunohistochemistry using 33 antibodies targeting molecules known to play a part in the development of various tumors. Overexpression of carbonic anhydrase IX (CAIX) and loss of AT-rich interactive domain-containing protein 1A (ARID1A), aldehyde dehydrogenase 1 (ALDH1), and CD44 expression in GA patients were significantly correlated with lymph node (LN) metastasis, advanced tumor stage, and poor prognosis...
2016: Journal of Environmental Pathology, Toxicology and Oncology
Andrea Moretti, Jianfeng Li, Stefano Donini, Robert W Sobol, Menico Rizzi, Silvia Garavaglia
The aldehyde dehydrogenase family 1 member A3 (ALDH1A3) catalyzes the oxidation of retinal to the pleiotropic factor retinoic acid using NAD+ . The level of ALDHs enzymatic activity has been used as a cancer stem cell marker and seems to correlate with tumour aggressiveness. Elevated ALDH1A3 expression in mesenchymal glioma stem cells highlights the potential of this isozyme as a prognosis marker and drug target. Here we report the first crystal structure of human ALDH1A3 complexed with NAD+ and the product all-trans retinoic acid (REA)...
October 19, 2016: Scientific Reports
Josep Martí-Solans, Olga V Belyaeva, Nuria P Torres-Aguila, Natalia Y Kedishvili, Ricard Albalat, Cristian Cañestro
The bloom of genomics is revealing gene loss as a pervasive evolutionary force generating genetic diversity that shapes the evolution of species. Outside bacteria and yeast, however, the understanding of the process of gene loss remains elusive, especially in the evolution of animal species. Here, using the dismantling of the retinoic acid metabolic gene network (RA-MGN) in the chordate Oikopleura dioica as a case study, we combine approaches of comparative genomics, phylogenetics, biochemistry, and developmental biology to investigate the mutational robustness associated to biased patterns of gene loss...
September 2016: Molecular Biology and Evolution
Mousumi Majumder, Xiping Xin, Ling Liu, Elena Tutunea-Fatan, Mauricio Rodriguez-Torres, Krista Vincent, Lynne-Marie Postovit, David Hess, Peeyush K Lala
Cancer stem-like cells (SLC) resist conventional therapies, necessitating searches for SLC-specific targets. We established that cyclo-oxygenase(COX)-2 expression promotes human breast cancer progression by activation of the prostaglandin(PG)E-2 receptor EP4. Present study revealed that COX-2 induces SLCs by EP4-mediated NOTCH/WNT signaling. Ectopic COX-2 over-expression in MCF-7 and SKBR-3 cell lines resulted in: increased migration/invasion/proliferation, epithelial-mesenchymal transition (EMT), elevated SLCs (spheroid formation), increased ALDH activity and colocalization of COX-2 and SLC markers (ALDH1A, CD44, β-Catenin, NANOG, OCT3/4, SOX-2) in spheroids...
September 2016: Stem Cells
Nathaniel B Goldstein, Maranke I Koster, Laura G Hoaglin, Michael J Wright, Steven E Robinson, William A Robinson, Dennis R Roop, David A Norris, Stanca A Birlea
To characterize the gene expression profile of regenerated melanocytes in the narrow band UVB (NBUVB)-treated vitiligo epidermis and their precursors in the hair follicle, we present here a strategy of RNA isolation from in situ melanocytes using human frozen skin. We developed a rapid immunostaining protocol using the NKI-beteb antibody, which labels differentiated and precursor melanocytes, followed by fluorescent laser capture microdissection. This technique enabled the direct isolation, from melanocyte and adjacent keratinocyte populations, of satisfactory quality RNA that was successfully amplified and analysed by qRT-PCR...
October 2016: Experimental Dermatology
A Unguryte, E Bernotiene, E Bagdonas, S Garberyte, N Porvaneckas, C Jorgensen
OBJECTIVE: To determine in human articular chondrocytes the activity of Aldehyde dehydrogenase (ALDH), which are reported as stem/progenitor cell marker in various adult tissues and evaluate gene expression of ALDH1A isoforms. DESIGN: ALDH activity was evaluated by flow cytometry with Aldefluor™ assay in cells, isolated from human osteoarthritic (OA) cartilage. Its coexpression with surface markers was identified. Cells were sorted according to ALDH activity, and gene expression in sorted populations (ALDH(+) and ALDH(-)) was analyzed by RTq-PCR with Taqman(®) assay...
May 2016: Osteoarthritis and Cartilage
Samuel L Arnold, Faith Stevison, Nina Isoherranen
Protein quantification based on peptides using LC-MS/MS has emerged as a promising method to measure biomarkers, protein drugs, and endogenous proteins. However, the best practices for selection, optimization, and validation of the quantification peptides are not well established, and the influence of different matrices on protein digestion, peptide stability, and MS detection has not been systematically addressed. The aim of this study was to determine how biological matrices affect digestion, detection, and stability of peptides...
January 5, 2016: Analytical Chemistry
Mingli Sun, Haishan Zhao, Qinghuan Xiao, Zhaojin Yu, Zhiguo Song, Weifan Yao, Hongtao Tang, Shu Guan, Feng Jin, Minjie Wei
This study investigated the expression of ALDH1A1 and β-catenin in breast cancer patients, and analyzed the correlation of their combined expression with clinicopathological features, chemotherapeutic responses, and prognosis of breast cancer patients. In total 276 human breast cancer tissues and 80 benign hyperplasia tissues were included. The expression of ALDH1A1 and β-catenin was examined using tissue microarray-based immunohistochemistry. ROC curve analysis was performed to determine an optimal cut-off score for the expression of ALDH1A1 and β-catenin, based on the survival status of breast cancer patients...
December 2015: Oncology Reports
Faith Stevison, Jing Jing, Sasmita Tripathy, Nina Isoherranen
Vitamin A (retinol) and its active metabolite, all-trans-retinoic acid (atRA), play critical roles in regulating the differentiation, growth, and migration of immune cells. Similarly, as critical signaling molecules in the regulation of the cell cycle, retinoids are important in cancers. Concentrations of atRA are tightly regulated in tissues, predominantly by the availability of retinol, synthesis of atRA by ALDH1A enzymes and metabolism and clearance of atRA by CYP26 enzymes. The ALDH1A and CYP26 enzymes are expressed in several cell types in the immune system and in cancer cells...
2015: Advances in Pharmacology
Chanchal Mandal, Ji Hyun Park, Hyung Tae Lee, Hyemyung Seo, Il Yup Chung, Ihn Geun Choi, Kyoung Hwa Jung, Young Gyu Chai
The objective of the present study was to investigate the changes in gene expression in the fetal brain (forebrain and hippocampus) caused by maternal binge alcohol consumption. Pregnant C57BL/6J mice were treated intragastrically with distilled phosphate-buffered saline (PBS) or ethanol (2.9 g/kg) from embryonic day (ED) 8-12. Microarray analysis revealed that a significant number of genes were altered at ED 18 in the developing brain. Specifically, in hippocampus, nuclear factor one alpha (Nfia) and three N-methyl-D-aspartate (Nmda) receptors (Nmdar1, Nmdar2b, and Nmdar2d) were down-regulated...
June 26, 2015: Neuroscience Letters
J Xi, J Yue, Z Yang
Retinoic acid (RA) plays a crucial role in cellular proliferation, differentiation, and apoptosis. The physiological activity of RA begins early in development and continues throughout an organism's life. RA distribution is tightly controlled by the RA synthetases ALDH1As and the metabolic enzymes CYP26s. We analyzed the expressions of ALDH1As and CYP26s in whole embryos during zebrafish (Danio rerio) development and in adult zebrafish organs, by quantitative reverse transcriptase polymerase chain reaction analysis...
April 27, 2015: Genetics and Molecular Research: GMR
Samuel L M Arnold, Travis Kent, Cathryn A Hogarth, Michael D Griswold, John K Amory, Nina Isoherranen
all-trans retinoic acid (atRA), the active metabolite of vitamin A, is an essential signaling molecule. Specifically the concentrations of atRA are spatiotemporally controlled in target tissues such as the liver and the testes. While the enzymes of the aldehyde dehydrogenase 1A family (ALDH1A) are believed to control the synthesis of atRA, a direct relationship between altered ALDH1A activity and tissue atRA concentrations has never been shown. To test whether inhibition of ALDH1A enzymes decreases atRA concentrations in a tissue specific manner, the potent ALDH1A inhibitor WIN 18,446 was used to inhibit ALDH1A activity in mice...
June 1, 2015: Biochemical Pharmacology
Samuel L Arnold, Travis Kent, Cathryn A Hogarth, Stefan Schlatt, Bhagwat Prasad, Michael Haenisch, Thomas Walsh, Charles H Muller, Michael D Griswold, John K Amory, Nina Isoherranen
Retinoic acid (RA), the active metabolite of vitamin A, is required for spermatogenesis and many other biological processes. RA formation requires irreversible oxidation of retinal to RA by aldehyde dehydrogenase enzymes of the 1A family (ALDH1A). While ALDH1A1, ALDH1A2, and ALDH1A3 all form RA, the expression pattern and relative contribution of these enzymes to RA formation in the testis is unknown. In this study, novel methods to measure ALDH1A protein levels and intrinsic RA formation were used to accurately predict RA formation velocities in individual human testis samples and an association between RA formation and intratesticular RA concentrations was observed...
February 2015: Journal of Lipid Research
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