keyword
https://read.qxmd.com/read/38515178/auranofin-repurposing-for-lung-and-pancreatic-cancer-low-ca12-expression-as-a-marker-of-sensitivity-in-patient-derived-organoids-with-potentiated-efficacy-by-akt-inhibition
#1
JOURNAL ARTICLE
Christophe Deben, Laurie Freire Boullosa, Felicia Rodrigues Fortes, Edgar Cardenas De La Hoz, Maxim Le Compte, Sofie Seghers, Marc Peeters, Steve Vanlanduit, Abraham Lin, Krijn K Dijkstra, Paul Van Schil, Jeroen M H Hendriks, Hans Prenen, Geert Roeyen, Filip Lardon, Evelien Smits
BACKGROUND: This study explores the repurposing of Auranofin (AF), an anti-rheumatic drug, for treating non-small cell lung cancer (NSCLC) adenocarcinoma and pancreatic ductal adenocarcinoma (PDAC). Drug repurposing in oncology offers a cost-effective and time-efficient approach to developing new cancer therapies. Our research focuses on evaluating AF's selective cytotoxicity against cancer cells, identifying RNAseq-based biomarkers to predict AF response, and finding the most effective co-therapeutic agents for combination with AF...
March 22, 2024: Journal of Experimental & Clinical Cancer Research: CR
https://read.qxmd.com/read/38514720/the-immune-regulation-and-therapeutic-potential-of-the-smad-gene-family-in-breast-cancer
#2
JOURNAL ARTICLE
Zhuo Chen, Yu Wang, Xiaodi Lu, Hong Chen, Yiran Kong, Liwei Rong, Guonian Wang
Breast cancer is a serious threat to human health. The transforming growth factor-β signaling pathway is an important pathway involved in the occurrence and development of cancer. The SMAD family genes are responsible for the TGF-β signaling pathway. However, the mechanism by which genes of the SMAD family are involved in breast cancer is still unclear. Therefore, it is necessary to investigate the biological roles of the SMAD family genes in breast cancer. We downloaded the gene expression data, gene mutation data, and clinical pathological data of breast cancer patients from the UCSC Xena database...
March 21, 2024: Scientific Reports
https://read.qxmd.com/read/38495982/viral-peptide-conjugates-for-metal-warhead-delivery-to-chromatin
#3
JOURNAL ARTICLE
Lucinda K Batchelor, Louis De Falco, Paul J Dyson, Curtis A Davey
The presence of heavy metal groups can endow compounds with unique structural and chemical attributes beneficial for developing highly potent therapeutic agents and effective molecular labels. However, metallocompound binding site specificity is a major challenge that dictates the level of off-site targeting, which is a limiting factor in finding safer and more effective metal-based drugs. Here we designed and tested a family of metallopeptide conjugates based on two different chromatin-tethering viral proteins and a drug being repurposed for cancer, the Au(i) anti-arthritic auranofin...
March 14, 2024: RSC Advances
https://read.qxmd.com/read/38450675/auranofin-loaded-chitosan-nanoparticles-demonstrate-potency-against-triple-negative-breast-cancer
#4
JOURNAL ARTICLE
Maame Abena O Afrifa, Jong H Kim, Kathryn A Pitton, Chibuzor Olelewe, Adedamola S Arojojoye, Douglas R Strachan, Mark A Suckow, Samuel G Awuah
Triple-negative breast cancer (TNBC) remains a clinical challenge due to molecular, metabolic, and genetic heterogeneity as well as the lack of validated drug targets. Thus, therapies or delivery paradigms are needed. Gold-derived compounds including the FDA-approved drug, auranofin have shown promise as effective anticancer agents against several tumors. To improve the solubility and bioavailability of auranofin, we hypothesized that the nanodelivery of auranofin using biodegradable chitosan modified polyethylene glycol (PEG) nanoparticles (NPs) will enhance anticancer activity against TNBC by comparing the best nanoformulation with the free drug...
March 7, 2024: ACS Applied Bio Materials
https://read.qxmd.com/read/38423669/combined-auranofin-and-celecoxib-suppresses-the-local-progression-and-pulmonary-metastases-of-osteosarcoma-in-vivo
#5
JOURNAL ARTICLE
Hideyuki Kinoshita, Seiko Kinoshita, Hiroto Kamoda, Yoko Hagiwara, Seiji Ohtori, Tsukasa Yonemoto
BACKGROUND/AIM: Osteosarcoma (OS) is a rare malignant tumor with a poor survival rate. Our previous study reported that auranofin (AUR), a thioredoxin reductase inhibitor, suppresses OS pulmonary metastases; however, the local progression of OS is not affected, in vivo. Nonetheless, the development of augmentation therapy with AUR to inhibit OS local progression remains challenging. Celecoxib (CE), an anti-inflammatory drug, potently enhances the therapeutic activity of AUR against colon cancer...
March 2024: Anticancer Research
https://read.qxmd.com/read/38423598/thioredoxin-reductase-inhibitor-suppresses-the-local-progression-of-rhabdomyosarcoma-with-pdx-models
#6
JOURNAL ARTICLE
Hideyuki Kinoshita, Seiko Kinoshita, Hiroto Kamoda, Yoko Hagiwara, Seiji Ohtori, Tsukasa Yonemoto
BACKGROUND/AIM: Chemoresistance in rhabdomyosarcoma (RMS) is associated with poor survival, necessitating the development of novel anticancer drugs. Auranofin (AUR), an anti-rheumatic drug, is a thioredoxin reductase (TXNRD) inhibitor with anticancer properties. Although patient-derived xenograft (PDX) models are essential for studying cancer biology, reports on sarcomas using the PDX model are scarce because of their rarity. This study aimed to investigate the effectiveness of AUR treatment in RMS using a PDX model to evaluate its impact on local progression...
2024: Cancer Genomics & Proteomics
https://read.qxmd.com/read/38397381/role-of-mitochondrial-ros-for-calcium-alternans-in-atrial-myocytes
#7
JOURNAL ARTICLE
Yuriana Oropeza-Almazán, Lothar A Blatter
Atrial calcium transient (CaT) alternans is defined as beat-to-beat alternations in CaT amplitude and is causally linked to atrial fibrillation (AF). Mitochondria play a significant role in cardiac excitation-contraction coupling and Ca signaling through redox environment regulation. In isolated rabbit atrial myocytes, ROS production is enhanced during CaT alternans, measured by fluorescence microscopy. Exogenous ROS (tert-butyl hydroperoxide) enhanced CaT alternans, whereas ROS scavengers (dithiothreitol, MnTBAP, quercetin, tempol) alleviated CaT alternans...
January 24, 2024: Biomolecules
https://read.qxmd.com/read/38390865/targeted-liposomes-sensitize-plastic-melanoma-to-ferroptosis-via-senescence-induction-and-coenzyme-depletion
#8
JOURNAL ARTICLE
Lanlan Fan, Panyu Du, Yaru Li, Xuefei Chen, Fang Liu, Yuning Liu, Alexey M Petrov, Xin Li, Zheng Wang, Yanjun Zhao
Ferroptotic cancer therapy has been extensively investigated since the genesis of the ferroptosis concept. However, the therapeutic efficacy of ferroptosis induction in heterogeneous and plastic melanoma has been compromised, because the melanocytic and transitory cell subpopulation is resistant to iron-dependent oxidative stress. Here, we report a phenotype-altering liposomal nanomedicine to enable the ferroptosis-resistant subtypes of melanoma cells vulnerable to lipid peroxidation via senescence induction...
February 23, 2024: ACS Nano
https://read.qxmd.com/read/38387331/inhibition-of-the-thioredoxin-system-for-radiosensitization-therapy-of-cancer
#9
REVIEW
Yisheng Cao, Xiedong Zhou, Qiuying Nie, Junmin Zhang
Radiotherapy (RT) stands as a cornerstone in the clinical armamentarium against various cancers due to its proven efficacy. However, the intrinsic radiation resistance exhibited by cancer cells, coupled with the adverse effects of RT on normal tissues, often compromises its therapeutic potential and leads to unwanted side effects. This comprehensive review aims to consolidate our understanding of how radiosensitizers inhibit the thioredoxin (Trx) system in cellular contexts. Notable radiosensitizers, including gold nanoparticles (GNPs), gold triethylphosphine cyanide ([Au(SCN) (PEt3 )]), auranofin, ceria nanoparticles (CONPs), curcumin and its derivatives, piperlongamide, indolequinone derivatives, micheliolide, motexafin gadolinium, and ethane selenide selenidazole derivatives (SeDs), are meticulously elucidated in terms of their applications in radiotherapy...
February 9, 2024: European Journal of Medicinal Chemistry
https://read.qxmd.com/read/38384327/photo-driven-in%C3%A2-situ-solidification-of-whole-cells-through-inhibition-of-trogocytosis-for-immunotherapy
#10
JOURNAL ARTICLE
Hao Liu, Ke Huang, Hao Zhang, Xiaohui Liu, Hui Jiang, Xuemei Wang
Achieving antitumor immunotherapy based on hybridization of multiple types of inactivated cells has attracted a lot of attention. However, the hybridized cells of disordered structure could result in the shedding of antigens and their transfer to immune cells, which suppresses tumor immunity through trogocytosis. Here, we report a strategy for in situ solidification of tumor whole cell by biomineralization for sustained stimulation of antitumor immunity. The near-infrared light was used to accelerate the breaking of Au=P bonds in auranofin, and the exposed Au atoms biomineralize at the secondary structure (β-corner) of the protein to form Au nanocrystals with in situ protein coronas in tumor cells...
2024: Research: a science partner journal
https://read.qxmd.com/read/38382865/protein-s-nitrosylation-is-involved-in-valproic-acid-promoted-neuronal-differentiation-of-adipose-tissue-derived-stem-cells
#11
JOURNAL ARTICLE
Kenta Kurokawa, Kazuyuki Sogawa, Takehito Suzuki, Yoko Miyazaki, Kazuaki Tanaka, Makoto Usami, Tatsuya Takizawa
Neuronal differentiation of adipose tissue-derived stem cells (ASCs) is greatly promoted by valproic acid (VPA) with cAMP elevating agents thorough NO signaling pathways, but its mechanism is not fully understood. In the present study, we investigate the involvement of protein S-nitrosylation in the VPA-promoted neuronal differentiation of ASCs. The whole amount of S-nitrosylated protein was increased by the treatment with VPA alone for three days in ASCs. An inhibitor of thioredoxin reductase (TrxR), auranofin, further increased the amount of S-nitrosylated protein and enhances the VPA-promoted neuronal differentiation in ASCs...
February 19, 2024: Nitric Oxide: Biology and Chemistry
https://read.qxmd.com/read/38370715/far-red-and-sensitive-sensor-for-monitoring-real-time-h-2-o-2-dynamics-with-subcellular-resolution-and-in-multi-parametric-imaging-applications
#12
Justin Daho Lee, Amanda Nguyen, Zheyu Ruby Jin, Aida Moghadasi, Chelsea E Gibbs, Sarah J Wait, Kira M Evitts, Anthony Asencio, Samantha B Bremner, Shani Zuniga, Vedant Chavan, Andy Williams, Netta Smith, Michael Regnier, Jessica E Young, David Mack, Elizabeth Nance, Patrick M Boyle, Andre Berndt
H 2 O 2 is a key oxidant in mammalian biology and a pleiotropic signaling molecule at the physiological level, and its excessive accumulation in conjunction with decreased cellular reduction capacity is often found to be a common pathological marker. Here, we present a red fluorescent Genetically Encoded H 2 O 2 Indicator (GEHI) allowing versatile optogenetic dissection of redox biology. Our new GEHI, oROS-HT, is a chemigenetic sensor utilizing a HaloTag and Janelia Fluor (JF) rhodamine dye as fluorescent reporters...
February 8, 2024: bioRxiv
https://read.qxmd.com/read/38349407/fda-approved-disulfiram-as-a-novel-treatment-for-aggressive-leukemia
#13
JOURNAL ARTICLE
Mawar Karsa, Lin Xiao, Emma Ronca, Angelika Bongers, Dayna Spurling, Ayu Karsa, Sandra Cantilena, Anna Mariana, Tim W Failes, Greg M Arndt, Laurence C Cheung, Rishi S Kotecha, Rosemary Sutton, Richard B Lock, Owen Williams, Jasper de Boer, Michelle Haber, Murray D Norris, Michelle J Henderson, Klaartje Somers
Acute leukemia continues to be a major cause of death from disease worldwide and current chemotherapeutic agents are associated with significant morbidity in survivors. While better and safer treatments for acute leukemia are urgently needed, standard drug development pipelines are lengthy and drug repurposing therefore provides a promising approach. Our previous evaluation of FDA-approved drugs for their antileukemic activity identified disulfiram, used for the treatment of alcoholism, as a candidate hit compound...
February 13, 2024: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://read.qxmd.com/read/38284132/s-se-oxidative-addition-to-auranofin-derivatives-a-dft-study
#14
JOURNAL ARTICLE
Hélio F Dos Santos, Diego F S Paschoal
Oxidative addition of the S-Se bond to Au(I) complexes is discussed for a series of 26 auranofin (AF) derivatives. AF and its analogues are Au(I) complexes with recognized anticancer activity that act by binding and inhibiting the thioredoxin reductase (TrxR) enzyme. Generally, the oxidative addition to Au(I) is a sluggish reaction under mild conditions ( i.e. , a high activation barrier - Δ H ‡ ), which is also verified here for AF, Δ H ‡ = 33.0 kcal mol-1 . However, we predicted that subtle changes in the AF ligands can make the process feasible under standard conditions...
January 29, 2024: Physical Chemistry Chemical Physics: PCCP
https://read.qxmd.com/read/38269508/auranofin-sensitizes-breast-cancer-cells-to-paclitaxel-mediated-cell-death-via-regulating-foxo3-nrf2-keap1-signaling-pathway
#15
JOURNAL ARTICLE
N Deepika, N Rajendra Prasad, T Radhiga
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor which acts as a regulator for cellular oxidative stress, and tightly regulated by Kelch-like ECH-associated protein 1 (Keap1). In this study, we found that auranofin and paclitaxel combination treatment increased TUNEL positive apoptotic cells and enhanced the DNA damage marker γ-H2AX in MCF-7 and MDA-MB-231 breast cancer cells. The immunoblotting analysis revealed the combination of auranofin and paclitaxel significantly increased the FOXO3 expression in a concentration dependent manner...
January 2024: Cell Biochemistry and Function
https://read.qxmd.com/read/38244050/study-of-metalation-of-thioredoxin-by-gold-i-therapeutic-compounds-using-combined-liquid-chromatography-capillary-electrophoresis-with-inductively-coupled-plasma-electrospray-ms-ms-detection
#16
JOURNAL ARTICLE
Mikel Bernabeu De Maria, Magdalena Matczuk, Diego Tesauro, Michele Saviano, Jacek Sikorski, Giovanni Chiappetta, Simon Godin, Joanna Szpunar, Ryszard Lobinski, Luisa Ronga
The reactivity of thioredoxin (Trx1) with the Au(I) drug auranofin (AF) and two therapeutic N-heterocyclic carbene (NHC)2 -Au(I) complexes (bis [1-methyl-3-acridineimidazolin-2-ylidene]gold(I) tetrafluoroborate (Au3BC) and [1,3-diethyl-4,5-bis(4methoxyphenyl)imidazol-2-ylidene]gold(I) (Au4BC)) was investigated. Direct infusion (DI) electrospray ionization (ESI) mass spectrometry (MS) allowed information on the structure, stoichiometry, and kinetics of formation of Trx-Au adducts. The fragmentation of the formed adducts in the gas phase gave insights into the exact Au binding site within the protein, demonstrating the preference for Trx1 Cys32 or Cys35 of AF or the (NHC)2 -Au(I) complex Au3BC, respectively...
January 20, 2024: Analytical and Bioanalytical Chemistry
https://read.qxmd.com/read/38218139/mercury-binding-to-proteins-disclosed-by-esi-ms-experiments-the-case-of-three-organomercurials
#17
JOURNAL ARTICLE
Andrea Geri, Stefano Zineddu, Lara Massai, Luisa Ronga, Ryszard Lobinski, Jürgen Gailer, Luigi Messori
Solution interactions of three organomercury compounds, i.e., methylmercury chloride, thimerosal and phenylmercury acetate, with a group of biochemically relevant proteins, namely cytochrome c (Cyt c), ribonuclease A (RNase A), carbonic anhydrase I (hCA I), superoxide dismutase (SOD), and serum albumin (HSA), were investigated using an established ESI MS approach. Temporal analysis of sample aliquots provided insight into the binding kinetics, while comparative analysis of the obtained mass spectra disclosed adduct formation of each mercurial with the tested proteins and the relative abundance of the species...
January 6, 2024: Journal of Inorganic Biochemistry
https://read.qxmd.com/read/38206030/gold-i-ion-and-the-phosphine-ligand-are-necessary-for-the-anti-toxoplasma-gondii-activity-of-auranofin
#18
JOURNAL ARTICLE
C I Ma, J A Tirtorahardjo, S S Schweizer, J Zhang, Z Fang, L Xing, M Xu, D A Herman, M T Kleinman, B S McCullough, A M Barrios, R M Andrade
Toxoplasmosis, caused by Toxoplasma gondii , is a devastating disease affecting the brain and the eyes, frequently affecting immunocompromised individuals. Approximately 60 million people in the United States are already infected with T. gondii , representing a population at-risk of developing toxoplasmosis. Recent advances in treating cancer, autoimmune diseases, and organ transplants have contributed to this at-risk population's exponential growth. Paradoxically, treatments for toxoplasmosis have remained the same for more than 60 years, relying on medications well-known for their bone marrow toxicity and allergic reactions...
January 11, 2024: Microbiology Spectrum
https://read.qxmd.com/read/38206016/the-mechanism-of-action-of-auranofin-analogs-in-b-cenocepacia-revealed-by-chemogenomic-profiling
#19
JOURNAL ARTICLE
Dustin T Maydaniuk, Brielle Martens, Sarah Iqbal, Andrew M Hogan, Neil Lorente Cobo, Anna Motnenko, Dang Truong, Sajani H Liyanage, Mingdi Yan, Gerd Prehna, Silvia T Cardona
The Burkholderia cepacia complex is a group of multidrug-resistant bacteria that can cause infections in the lungs of people with the autosomal recessive disease, cystic fibrosis. Specifically, the bacterium Burkholderia cenocepacia can cause severe infections, reducing lung function and leading to a devastating type of sepsis, cepacia syndrome. This bacterium currently does not have an accepted antibiotic treatment plan because of the wide range of antibiotic resistance. Here, we further the research on auranofin analogs as antimicrobials by finding the mechanism of action of these potent bactericidal compounds, using a powerful technique called BarSeq, to find the global response of the cell when exposed to an antimicrobial...
January 11, 2024: Microbiology Spectrum
https://read.qxmd.com/read/38193717/the-nonessential-amino-acid-cysteine-is-required-to-prevent-ferroptosis-in-acute-myeloid-leukemia
#20
JOURNAL ARTICLE
Alan Cunningham, Lieve L Oudejans, Marjan Geugien, Diego Antonio Pereira-Martins, Albertus T J Wierenga, Ayşegül Erdem, Dominique Sternadt, Gerwin Huls, Jan Jacob Schuringa
Cysteine is a nonessential amino acid required for protein synthesis, the generation of the antioxidant glutathione, and for synthesizing the nonproteinogenic amino acid taurine. Here, we highlight the broad sensitivity of leukemic stem and progenitor cells to cysteine depletion. By CRISPR/CRISPR-associated protein 9-mediated knockout of cystathionine-γ-lyase, the cystathionine-to-cysteine converting enzyme, and by metabolite supplementation studies upstream of cysteine, we functionally prove that cysteine is not synthesized from methionine in acute myeloid leukemia (AML) cells...
January 9, 2024: Blood Advances
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