Dexamethasone is a synthetic glucocorticoid frequently used to suppress side-effects of anticancer chemotherapy. In the present study, we showed that dexamethasone treatment leads to concentration-dependent downregulation of cancer-associated marker, carbonic anhydrase IX (CA IX), at the level of promoter activity, mRNA and protein expression in 2D and 3D cancer cell models. The effect of dexamethasone on CA IX expression under hypoxic conditions is predominantly mediated by impaired transcriptional activity and decreased protein level of the main hypoxic transcription factor HIF-1α. In addition, CA9 downregulation can be caused by protein-protein interactions between activated glucocorticoid receptors, major effectors of glucocorticoid action, and transcription factors that trigger CA9 transcription (e.g. AP-1). Moreover, we identified a potential NF-κB binding site in the CA9 promoter and propose the involvement of NF-κB in the dexamethasone-mediated inhibition of CA9 transcription. As high level of CA IX is often linked to aggressive tumor behavior, poor prognosis and chemo- and radiotherapy resistance, uncovering its reduction after dexamethasone treatment and implication of additional regulatory mechanisms can be relevant for the CA IX-related clinical applications.
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http://dx.doi.org/10.3892/ijo.2016.3621 | DOI Listing |
Aim: Human carbonic anhydrases (hCAs) are involved in many physiological processes including respiration, pH control, ion transport, bone resorption, and gastric fluid secretion. Recently, CA IX and CA XII have been studied for their role in cancer diseases, motivating the design of inhibitors of these isoforms.
Material And Method: Here, we used the tail approach to design a new series of monoaryl () and bicyclic () benzensulfonamide derivatives CA IX and CA XII inhibitors.
Front Immunol
January 2025
First Department of Pediatrics, Weifang People's Hospital Affiliated to Shandong Second Medical University, Weifang, China.
Autoimmune cerebellar ataxia (ACA) is a cerebellar syndrome induced by autoimmune reactions and its onset is induced by malignant tumors, prodromic infection, and gluten allergy. Its clinical symptoms include gait disorder, limb ataxia, dysarthria, and dysphagia. According to , the diagnosis of ACA is based on the following points: 1.
View Article and Find Full Text PDFBioact Mater
May 2025
Bioscience and Biomedical Engineering Thrust, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, 511400, China.
Tumor microenvironment governs various therapeutic tolerability of cancer such as ferroptosis and immunotherapy through rewiring tumor metabolic reprogramming like Warburg metabolism. Highly expressed carbonic anhydrases (CA) in tumor that maintaining the delicate metabolic homeostasis is thus the most potential target to be modulated to resolve the therapeutic tolerability. Hence, in this article, a self-healable and pH-responsive spermidine/ferrous ion hydrogel loaded with CA inhibitor (acetazolamide, ACZ) and glucose oxidase (ACZ/GOx@SPM-HA Gel) was fabricated through the Schiff-base reaction between spermidine-dextran and oxidized hyaluronic acid, along with ferrous coordination.
View Article and Find Full Text PDFJ Sci Food Agric
January 2025
Bee and Natural Products R&D and P&D Application and Research Center, Bingöl University, Bingöl, Turkey.
Background: Phlomis capitata is an endemic species of flowering aromatic and medicinal plant in the family Lamiaceae, native to regions of the Mediterranean and nearby areas. Understanding the chemical compounds present in P. capitata can reveal potential medicinal properties.
View Article and Find Full Text PDFJ Fish Biol
January 2025
Laboratory of Ecophysiology and Molecular Evolution, National Institute for Amazonian Research, Manaus, Brazil.
Optical characterization of dissolved organic carbon (DOC) freshly collected from the circumneutral "white water" of the Rio Solimoes revealed that it had lower aromaticity, lower molecular weight, and a greater autochthonous content than DOC from the acidic "black water" of the Rio Negro. The tambaqui (Colossoma macropomum), a characid member of the Serrasalmidae, is a model neotropical fish that migrates annually between the two rivers. We analysed ionoregulatory responses of the tambaqui over 24 h in ion-poor water at pH 7.
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