Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm of the hematopoietic stem cell characterized by presence of the oncoprotein BCR-ABL1, which have constitutive tyrosine kinase activity. BCR-ABL1 activation induces aurora kinase A (AURKA) and aurora kinase B (AURKB) expression, which are serine-threonine kinases that play an important function in chromosome alignment, segregation and cytokinesis during mitosis. Acquisition of resistance to tyrosine kinase inhibitors has emerged as a problem for CML patients and the identification of novel targets with an important contribution for CML phenotype is of interest. In the present study, we explored the cellular effects of reversine, an AURKA and AURKB inhibitor, in the BCR-ABL1+ K562 cells. Our results indicate that reversine reduces AURKA and AURKB expression, leads to reduction of cell viability and increased apoptosis in a dose- and time-dependent manner, as well as, induces mitotic catastrophe in K562 cells. Our preclinical study establishes that reversine presents an effective antileukemia activity against K562 cells and provide new insights on anticancer opportunities for CML.
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http://dx.doi.org/10.1016/j.leukres.2016.06.011 | DOI Listing |
Nucleic Acids Res
January 2025
Department of Orthopaedics and Traumatology, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong SAR, China.
Mammalian genome is hierarchically organized by CTCF and cohesin through loop extrusion mechanism to facilitate the organization of topologically associating domains (TADs). Mounting evidence suggests additional factors/mechanisms exist to orchestrate TAD formation and maintenance. In this study, we investigate the potential role of RNA-binding proteins (RBPs) in TAD organization.
View Article and Find Full Text PDFAnticancer Drugs
January 2025
Department of Laboratory Medicine, Fujian Medical University Union Hospital, Fuzhou, China.
Imatinib mesylate (IM) is a first-line therapy for chronic myeloid leukemia (CML) and exhibits good therapeutic effects, but not in all patients with CML owing to drug resistance. Our previous study showed that Cyr61 plays a key role in IM resistance in CML cells. Paeoniflorin (PF) is a bioactive compound isolated from the traditional Chinese medicine Paeonia lactiflora Pall that displays anticancer activity.
View Article and Find Full Text PDFPharmaceuticals (Basel)
November 2024
Laboratory of Nanobiotechnologies, Saint-Petersburg National Research Academic University of the Russian Academy of Sciences, Saint Petersburg 194021, Russia.
: A series of spiro-fused heterocyclic compounds containing cyclopropa[a]pyrrolizidine-2,3'-oxindole and 3-spiro[3-azabicyclo[3.1.0]-hexane]oxindole frameworks were synthesized and studied for their in vitro antiproliferative activity against human erythroleukemia (K562), cervical carcinoma (HeLa), acute T cell leukemia (Jurkat), melanoma (Sk-mel-2) and breast cancer (MCF-7) as well as mouse colon carcinoma (CT26) cell lines.
View Article and Find Full Text PDFMolecules
December 2024
Laboratory of Advanced Materials in Biopharmaceutics and Technics, Institute of Chemistry, Moldova State University, MD-2009 Chisinau, Moldova.
Ten coordination compounds, [Cu(L)Cl] (), [Cu(L)NO] (), [Cu(L)Cl] (C3), [Cu(L)NO] (), [Cu(L)Cl] (), [Cu(L)NO] (), [Cu(L)NO] (), [Cu(L)Cl] (), [Cu(L)Cl] (), and [Cu(L)NO] (), containing pyridine derivatives of -methoxyphenyl-thiosemicarbazones were synthesized and characterized. The molecular structure of four compounds was investigated using single crystal X-ray diffraction. Spectral analysis techniques such as FT-IR, H NMR, C NMR, elemental analysis, and molar conductivity were used for all the synthesized compounds.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Biosciences, Biotechnology and Environment, University of Bari Aldo Moro, 70125 Bari, Italy.
Mutations in the SLC25A38 gene are responsible for the second most common form of congenital sideroblastic anemia (CSA), a severe condition for which no effective treatment exists. We developed and characterized a K562 erythroleukemia cell line with markedly reduced expression of the SLC25A38 protein (A38-low cells). This model successfully recapitulated the main features of CSA, including reduced heme content and mitochondrial respiration, increase in mitochondrial iron, ROS levels and sensitivity to oxidative stress.
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