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Stephen Keysar, Justin Eagles, Bettina Miller, Brian C Jackson, Farshad N Chowdhury, Julie Reisinger, Tugs-Saikhan Chimed, Phuong N Le, J Jason Morton, Hilary Somerset, Marileila Varella-Garcia, Aik-Choon Tan, John I Song, Daniel W Bowles, Mary E Reyland, Antonio Jimeno
PURPOSE: Salivary gland cancers (SGC) frequently present with distant metastases many years after diagnosis, suggesting a cancer stem cell (CSC) subpopulation that initiates late recurrences; however current models are limited both in their availability and suitability to characterize these rare cells. EXPERIMENTAL DESIGN: Patient-derived xenografts (PDX) were generated by engrafting patient tissue onto nude mice from one acinic cell carcinoma (AciCC), four adenoid cystic carcinoma (ACC), and three mucoepidermoid carcinoma (MEC) cases, which were derived from successive relapses from the same MEC patient...
March 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Shaomin Yan, Guang Wu
It is curious that East Asian women have a low incidence and mortality of ovarian cancer in various epidemiological studies. Although different explanations were given, they appear unsubstantial. We notice that East Asian population usually are inactive aldehyde dehydrogenase 2 mutation (ALDH2 * 2) carriers, and ALDH plays an important role in the resistance of ovarian cancer to chemotherapeutics, especially in ovarian cancer stem cells. Therefore, we hypothesize whether ALDH2 mutation is the major reason for low incidence and mortality of ovarian cancer in East Asian women, and use the evidence from literature, transcriptomic data with average 5-year overall survival to confirm our hypothesis...
February 23, 2018: Oncotarget
Xi Wu, Xue Xue, Lihui Wang, Wenjing Wang, Jian Han, Xiaoxue Sun, Haotian Zhang, Yueyang Liu, Xiaohang Che, Jingyu Yang, Chunfu Wu
Autophagy, a cellular survival mechanism, is thought to allow the recycling of cellular breakdown products when cancer cells are subjected to chemotherapy, thus decreasing drug-induced apoptosis. Disulfiram (DSF), a drug widely used to control alcoholism, possesses anticancer activity by inducing apoptosis in vitro and in vivo in a copper (Cu)-dependent manner. Our previous studies proved that DSF/Cu exerts increased anti-tumor effects on non-small cell lung cancer (NSCLC) xenograft models, and inhibits NSCLC recurrence driven by ALDH-positive cancer stem cells...
March 13, 2018: European Journal of Pharmacology
Marwa M Abu-Serie
Liver cancer is mainly originated by cancer stem cells (CSCs). Due to difference in pH between normal and tumor cell microenvironments, targeting hepatic CSCs exploiting pH-dependent charge switchable nanoparticles (NPs) is extremely required to limit nonselective toxicity to normal hepatocytes (NHCs) and to completely eliminate the root of cancer origin. In this study, NPs were prepared from cationic chitosan and then coated with anionic albumin namely uncoated and coated NPs, respectively. Both NPs were loaded with diethyldithiocarbamate (DDC) which is an inhibitor of the critical enzyme, aldehyde dehydrogenase (ALDH) 1A1, for CSCs survival...
March 15, 2018: Scientific Reports
Joo Yeon Seok, Jina Yang, Sang Jin Choi, Hyun Gyu Lim, Un Jong Choi, Kyung-Jin Kim, Sunghoon Park, Tae Hyeon Yoo, Gyoo Yeol Jung
3-Hydroxypropionic acid (3-HP) is an important platform chemical, and biological production of 3-HP from glycerol as a carbon source using glycerol dehydratase (GDHt) and aldehyde dehydrogenase (ALDH) has been revealed to be effective because it involves a relatively simple metabolic pathway and exhibits higher yield and productivity than other biosynthetic pathways. Despite the successful attempts of 3-HP production from glycerol, the biological process suffers from problems arising from low activity and inactivation of the two enzymes...
March 12, 2018: Metabolic Engineering
Adejoke N Kolawole, Valentine T Akinladejo, Olusola O Elekofehinti, Afolabi C Akinmoladun, Ayodele O Kolawole
Aldehyde dehydrogenases (ALDHs) are a diverse family of enzymes that catalyze the NAD(P)+ -dependent detoxification of toxic aldehyde compounds. ALDHs are also involved in non-enzymatic ligand binding to endobiotics and xenobiotics. Here, the enzyme crucial non-canonical and non-catalytic interaction with kolaflavanone, a component of kolaviron, and a major bioflavonoid isolated from Garcinia kola (Bitter kola) was characterized by various spectroscopic and in silico approaches under stimulated physiological condition...
February 27, 2018: Bioorganic Chemistry
Tagnon D Missihoun, Simeon O Kotchoni
Aldehyde dehydrogenase enzymes (ALDHs) catalyse the oxidation of a broad range of aliphatic and aromatic aldehydes to their corresponding carboxylic acids using NAD+ or NADP+ as cofactors. In our article published in Scientific Reports, we demonstrated that mutations in Arabidopsis ALDH3I1 and ALDH7B4 genes altered the cellular contents of NAD(P)H, the total as well as the reduction state of glutathione; and decreased the efficiency of photosynthesis, thus placing ALDH activity as an important source of reducing power for cellular redox homeostasis...
March 9, 2018: Plant Signaling & Behavior
Małgorzata Iciek, Magdalena Górny, Anna Bilska-Wilkosz, Danuta Kowalczyk-Pachel
Aldehyde dehydrogenase (ALDH) catalyzes the critical step of ethanol metabolism, i.e. transformation of toxic acetaldehyde to acetic acid. It is a redox sensitive protein with the key Cys in its active site. Recently, it has been documented that activity of some proteins can be modified by sulfur-containing molecules called reactive sulfur species leading to the formation of hydro- persulfides. The aim of the present study was to examine whether ALDH activity can be modified in this way. Studies were performed in vitro using yeast ALDH and various reactive sulfur species, including Na2 S, GSSH, K2 Sx , Na2 S2 O3 , and garlic-derived allyl sulfides...
March 9, 2018: Acta Biochimica Polonica
Sofia Frändberg, Susann Li, Cecilia Boreström, Jan Holgersson, Lars Palmqvist
BACKGROUND: Cord blood units (CBUs) are processed, frozen, and thawed before use in hematopoietic stem cell (HSC) transplantation. The manipulations affect HSC functionality, that is, induce apoptosis and reduce viability. HSC content, commonly expressed as CBU potency, that is, the expected ability of a CBU to restore hematopoiesis, is traditionally approximated through viable CD34+ cells and the colony-forming unit (CFU) cell cultivation assay. Alternative approaches, for example, the aldehyde dehydrogenase (ALDH) enzyme-based assay, are also forthcoming...
March 7, 2018: Transfusion
Xiangchou Yang, Rongxin Yao, Hong Wang
Studies employing mouse transplantation have illustrated the role of aldehyde dehydrogenase (ALDH) defining hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs). Besides being a molecular marker, ALDH mediates drug resistance in AML, which induces poor prognosis of the patients. In AML patients, either CD34+ ALDHbr population or CD34+ CD38- ALDHint population was found to denote LSCs and minimal residual disease (MRD). A bunch of reagents targeting ALDH directly or indirectly have been evaluated. ATRA, disulfiram, and dimethyl ampal thiolester (DIMATE) are all shown to be potential candidates to open new perspective for AML treatment...
2018: BioMed Research International
Yun-Jung Choi, Sangiliyandi Gurunathan, Jin-Hoi Kim
The use of graphene to target and eliminate cancer stem cells (CSCs) is an alternative approach to conventional chemotherapy. We show the biomolecule-mediated synthesis of reduced graphene oxide-silver nanoparticle nanocomposites (rGO-Ag) using R-phycoerythrin (RPE); the resulting RPE-rGO-Ag was evaluated in human ovarian cancer cells and ovarian cancer stem cells (OvCSCs). The synthesized RPE-rGO-Ag nanocomposite (referred to as rGO-Ag) was characterized using various analytical techniques. rGO-Ag showed significant toxicity towards both ovarian cancer cells and OvCSCs...
March 1, 2018: International Journal of Molecular Sciences
Wenzhi Shen, Junling Xie, Shuangtao Zhao, Renle Du, Xiaohe Luo, Huiwen He, Shan Jiang, Na Hao, Chong Chen, Chunlei Guo, Yanhua Liu, Yanan Chen, Peiqing Sun, Shengyong Yang, Na Luo, Rong Xiang, Yunping Luo
In this study, we present a medium throughput siRNA screen platform to identify inflammation genes that regulate cancer cell stemness. We identified several novel candidates that decrease OCT4 expression and reduce the ALDH + subpopulation both of which are characteristic of stemness. Furthermore, one of the novel candidates ICAM3 up-regulates in the ALDH + subpopulation, the side population and the developed spheres. ICAM3 knockdown reduces the side population, sphere formation and chemo-resistance in MDA-MB-231 human breast cancer cells and A549 lung cancer cells...
February 22, 2018: Cancer Letters
Yun Zhu, Cindy Wang, Scott A Becker, Katie Hurst, Lourdes M Nogueira, Victoria J Findlay, E Ramsay Camp
Epithelial-to-mesenchymal transition (EMT) has been closely linked with therapy resistance and cancer stem cells (CSCs). However, EMT pathways have proven challenging to therapeutically target. MicroRNA 145 (miR-145) targets multiple stem cell transcription factors and its expression is inversely correlated with EMT. Therefore, we hypothesized that miR-145 represents a therapeutic target to reverse snail family transcriptional repressor 1 (SNAI1)-mediated stemness and radiation resistance (RT). Stable expression of SNAI1 in DLD1 and HCT116 cells (DLD1-SNAI1; HCT116-SNAI1) increased expression of Nanog and decreased miR-145 expression compared to control cells...
March 7, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Xiuxiu Wang, Min Liu, Chen Zhang, Shangshang Li, Qihang Yang, Jianjun Zhang, Zhiyuan Gong, Jiandong Han, Le Jia
This work was to examine the antioxidation in vitro and hepatoprotective effects of enzyme-extracted Oudemansiella radiata polysaccharides (En-OPS) on alcohol-induced liver damage in mice. The antioxidant activities were determined according to the scavenging effects of En-OPS on hydroxyl, superoxide, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, and the level of reducing power. En-OPS showed hepatoprotective activities on decreasing the serum levels of aspertate aminotransferase (AST), alamine aminotransferase (ALT), and alkaline phosphatase (ALP), as well as hepatic lipid levels of total cholesterol (TC) and triacylglycerols (TG)...
February 23, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Haengki Park, Kenji Ohshima, Satoshi Nojima, Shinichiro Tahara, Masako Kurashige, Yumiko Hori, Daisuke Okuzaki, Naoki Wada, Jun-Ichiro Ikeda, Eiichi Morii
Adenylosuccinate lyase (ADSL) is an enzyme that plays important roles in de novo purine synthesis. Although ADSL was reported to be upregulated in various malignancies, such as colorectal, breast, and prostate cancer, as well as gliomas, the mechanism by which elevated ADSL expression contributes to cancer has not been elucidated. We previously performed a shotgun proteomics analysis to characterize specific proteins associated with the properties of the aldehyde dehydrogenase (ALDH)-high cell population, which was reported to be involved in tumorigenic potential, and showed that ADSL expression is upregulated in the ALDH-high population of endometrial cancer...
February 21, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Jing Ma, Joseph Salamoun, Peter Wipf, Robert Edwards, Bennett Van Houten, Wei Qian
Cancer stem cell-like cells (CSC-LCs) contribute to drug resistance and recurrence of ovarian cancer. Strategies that can eradicate CSC-LCs are expected to substantially improve the outcome of ovarian cancer treatment. We have previously identified a class of thioxodihydroquinazolinone small molecules, which have strong synergistic antitumor activity with platinum drugs, the standard chemotherapeutic agents for ovarian cancer treatment. In the current study, using the activity of aldehyde dehydrogenase (ALDH) as a marker of CSC-LCs, we demonstrated that the combination of thioxodihydroquinazolinone compound 19 with cisplatin is able to diminish ALDH-high CSC-LC populations in both platinum-resistant ovarian cancer cell lines and primary ovarian cancer cells from metastatic ascites of a cisplatin-resistant patient...
January 19, 2018: Oncotarget
Laura W Bowers, Emily L Rossi, Shannon B McDonell, Steven S Doerstling, Subreen A Khatib, Claire G Lineberger, Jody E Albright, Xiaohu Tang, Linda A deGraffenried, Stephen D Hursting
Obesity is associated with poor prognosis in triple-negative breast cancer (TNBC). Preclinical models of TNBC were used to test the hypothesis that increased leptin signaling drives obesity-associated TNBC development by promoting cancer stem cell (CSC) enrichment and/or epithelial-to-mesenchymal transition (EMT). MMTV-Wnt-1 transgenic mice, which develop spontaneous basal-like, triple-negative mammary tumors, received either a control diet (10% kcal from fat) or a diet-induced obesity regimen (DIO, 60% kcal from fat) for up to 42 weeks (n=15/group)...
February 16, 2018: Molecular Cancer Research: MCR
Bruna Corominas-Faja, Elisabet Cuyàs, Jesús Lozano-Sánchez, Sílvia Cufí, Sara Verdura, Salvador Fernández-Arroyo, Isabel Borrás-Linares, Begoña Martin-Castillo, Ángel G Martin, Ruth Lupu, Alfons Nonell-Canals, Melchor Sanchez-Martinez, Vicente Micol, Jorge Joven, Antonio Segura-Carretero, Javier A Menendez
Targeting tumor-initiating, drug-resistant populations of cancer stem cells (CSC) with phytochemicals is a novel paradigm for cancer prevention and treatment. We herein employed a phenotypic drug discovery approach coupled to mechanism-of-action profiling and target deconvolution to identify phenolic components of extra virgin olive oil (EVOO) capable of suppressing the functional traits of CSC in breast cancer (BC). In vitro screening revealed that the secoiridoid decarboxymethyl oleuropein aglycone (DOA) could selectively target sub-populations of epithelial-like, aldehyde dehydrogenase (ALDH)-positive and mesenchymal-like, CD44+CD24-/low CSC...
February 14, 2018: Carcinogenesis
Seyoung Lee, Dong Jun Park, Jihee Yoon, Seung Hyuck Bang, Yang-Hoon Kim, Jiho Min
Formaldehyde is a toxic compound due to its ability to react with proteins, nucleic acids and lipids and is the primary cause of nasopharyngeal cancer and sick building syndrome (SBS). Aldehyde dehydrogenases (ALDHs) are able to oxidize aldehyde substrates and maintain cellular homeostasis by metabolic reactions in prokaryotic and eukaryotic cells. ALDHs catalyze the conversions of various aldehydes to carboxylic acids using NAD or NADP as a cofactor. In this study, we designed a method for using aldehyde dehydrogenase 6 (ALD6) from recombinant Saccharomyces cerevisiae to reduce formaldehyde...
April 1, 2018: Journal of Nanoscience and Nanotechnology
Timothy Henderson, Mingyi Chen, Morgan A Darrow, Chin-Shang Li, Chi-Lu Chiu, Arta M Monjazeb, William J Murphy, Robert J Canter
BACKGROUND: Cancer stem cells (CSCs) have been shown to resist chemotherapy and promote metastasis after cytotoxic therapies. We sought to determine if the expression of CSC markers (aldehyde dehydrogenase [ALDH], CD44, and epidermal growth factor receptor [EGFR]) predicted outcomes in soft-tissue sarcoma (STS) patients. METHODS: We queried an institutional database of 23 STS patients and evaluated immunohistochemical expression of CSC markers ALDH, CD44, and EGFR...
March 2018: Journal of Surgical Research
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