The inhibition of bromo- and extraterminal domains (BET) has shown an anti-proliferative effect in triple negative breast cancer (TNBC). In this article we explore mechanisms of resistance to BET inhibitors (BETi) in TNBC, with the aim of identifying novel ways to overcome such resistance. Two cellular models of acquired resistance to the BET inhibitor JQ1 were generated using a pulsed treatment strategy. MTT, colony formation, and cytometry assays revealed that BETi-resistant cells were particularly sensitive to PLK1 inhibition. Targeting of the latter reduced cell proliferation, especially in resistant cultures. Quantitative PCR analysis of a panel of mitotic kinases uncovered an increased expression of AURKA, TTK, and PLK1, confirmed by Western blot. Only pharmacological inhibition of PLK1 showed anti-proliferative activity on resistant cells, provoking G2/M arrest, increasing expression levels of cyclin B, pH3 and phosphorylation of Bcl-2 proteins, changes that were accompanied by induction of caspase-dependent apoptosis. JQ1-resistant cells orthotopically xenografted into the mammary fat pad of mice led to tumours that retained JQ1-resistance. Administration of the PLK1 inhibitor volasertib resulted in tumour regression. These findings open avenues to explore the future use of PLK1 inhibitors in the clinical setting of BETi-resistant patients.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.canlet.2020.06.020 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Overview of the epigenetic/cytotoxic dual-target inhibitors for cancer therapy.
Eur J Med Chem
January 2025
School of Medical and Information Engineering, School of Pharmacy, Gannan Medical University, Ganzhou, 341000, PR China; Jiangxi Provincial Key Laboratory of Tissue Engineering, Gannan Medical University, Ganzhou, 341000, PR China. Electronic address:
Epigenetic dysregulation plays a pivotal role in the initiation and progression of various cancers, influencing critical processes such as tumor growth, invasion, migration, survival, apoptosis, and angiogenesis. Consequently, targeting epigenetic pathways has emerged as a promising strategy for anticancer drug discovery in recent years. However, the clinical efficacy of epigenetic inhibitors, such as HDAC inhibitors, has been limited, often accompanied by resistance.
View Article and Find Full Text PDFSynthesis Strategy Toward Minimizing Adventitious Oxygen Contents in the Mechanochemically Made Semiconductor Kesterite CuZnSnS Nanopowders.
Materials (Basel)
December 2024
Faculty of Energy and Fuels, AGH University, al. Mickiewicza 30, 30 059 Kraków, Poland.
A multipronged approach to the refined mechanochemical synthesis of the semiconductor kesterite CuZnSnS with minimal quantities of adventitious oxygen as well as to optimizing handling procedures from that angle is described. Three precursor systems are used to provide a pool of freshly made cubic prekesterite nanopowders with no semiconductor properties and the thermally annealed at 500 °C tetragonal kesterite nanopowders of the semiconductor. Based on the previously reported high propensity of such nanopowders to long-term deteriorating oxidation in ambient air, suitable modifications of all crucial synthesis steps are implemented, which are directed toward excluding or limiting the materials' exposure to air.
View Article and Find Full Text PDFPeroxydisulfate activation by synergized modified AgCuFeO@GO nanoparticle electrode with anchored MnO in cefixime three-dimensional electrochemical degradation: Optimization and mechanisms.
J Environ Manage
January 2025
Environmental Health Engineering Research Center, Kerman University of Medical Sciences, Kerman, Iran. Electronic address:
Cefixime (CFX) is a potent antibiotic against gram-positive and gram-negative bacteria that resists degradation and typical removal procedures. This research aimed to synthesize a modified AgCuFeO@GO nanoparticle electrode with anchored MnO for removing CFX by three-dimensional electrochemical oxidation. The physical and chemical characteristics of the nanocomposite were evaluated using various techniques, including FESEM, XRD, EDS-mapping, FTIR, BET, VSM, and TGA.
View Article and Find Full Text PDFIdentification and analysis of major latex protein () family genes in responsive to infection by RNA-seq approaches.
Front Plant Sci
December 2024
College of Landscape Engineering, Suzhou Polytechnic Institute of Agriculture, Suzhou, China.
Roses () are among the most cherished ornamental plants globally, yet they are highly susceptible to infections by , the causative agent of gray mold disease. Here we inoculated the resistant rose variety 'Yellow Leisure Liness' with to investigate its resistance mechanisms against gray mold disease. Through transcriptome sequencing, we identified 578 differentially expressed genes (DEGs) that were significantly upregulated at 24, 48, and 72 hours post-inoculation, with these genes significantly enriched for three defense response-related GO terms.
View Article and Find Full Text PDFIdentification of potential molecular markers for detection of lengthy chilled storage of L. fruit.
Heliyon
December 2024
Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy.
Low temperature is the main strategy to preserve fruit quality post-harvest, in the supply chain. Low temperatures reduce the respiration, ethylene emission, and enzymatic activities associated with senescence. Unfortunately, peaches are sensitive to low temperatures if exposed for long periods, resulting in physiological disorders that can compromise commercial quality.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!