Purpose: Breast cancer is the most common cancer in women. Triple-negative breast cancer (TNBC) is an aggressive disease with poor outcomes. TNBC lacks effective targeted treatments, and the development of drug resistance limits the effectiveness of chemotherapy. It is crucial to identify new drugs that can enhance the efficacy of traditional chemotherapy to reduce drug resistance and side effects.
Methods: TNBC cell lines, MDA-MB-231 and Hs 578T, and a normal cell line, MCF-10 A, were included in this study. The cells were treated with gallium maltolate (GaM), and their transcriptome was analyzed. Ferroptosis and nucleolar stress markers were detected by qPCR, western blotting, fluorescence microscopy, and flow cytometry. The impairment of ribosome synthesis was evaluated by northern blotting and sucrose gradients.
Results: GaM triggered cell death via apoptosis and ferroptosis. In addition, GaM impaired translation and activated nucleolar stress. Cisplatin (DDP) is a chemotherapeutic agent for advanced breast cancer. While single treatment with GaM or DDP at low concentrations did not impact cell growth, co-administration enhanced cell death in TNBC but not in normal breast cells. The enhancement of ferroptosis and nucleolar stress could be observed in TNBC cell lines after co-treatment.
Conclusions: These results suggest that GaM synergizes with cisplatin via activation of nucleolar stress and ferroptosis in human breast carcinoma cells. GaM is marginally toxic to normal cells but impairs the growth of TNBC cell lines. Thus, GaM has the potential to be used as a therapeutic agent against TNBC.
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http://dx.doi.org/10.1007/s13402-023-00804-x | DOI Listing |
Mol Biol Cell
December 2024
Dept. of Genetics.
Ribosome biogenesis (RB) is an intricate and evolutionarily conserved process that takes place mainly in the nucleolus and is required for eukaryotic cells to maintain homeostasis, grow in size, and divide. Our laboratory has identified the NUF2 protein, part of the mitotic kinetochore, in a genome-wide siRNA screen for proteins required for making ribosomes in MCF10A human breast epithelial cells (Farley-Barnes, 2018). After rigorous validation and using several biochemical and cell-based assays, we find a role for NUF2 in pre-rRNA transcription, the primary and rate-limiting step of RB.
View Article and Find Full Text PDFMol Cancer
December 2024
Centre de Recherche des Cordeliers, Equipe Labellisée par la Ligue Contre le Cancer, Université de Paris, Institut Universitaire de France, Sorbonne Université, Inserm U1138, Paris, France.
Background: Immunogenic cell death (ICD) inducers are often identified in phenotypic screening campaigns by the release or surface exposure of various danger-associated molecular patterns (DAMPs) from malignant cells. This study aimed to streamline the identification of ICD inducers by leveraging cellular morphological correlates of ICD, specifically the condensation of nucleoli (CON).
Methods: We applied artificial intelligence (AI)-based imaging analyses to Cell Paint-stained cells exposed to drug libraries, identifying CON as a marker for ICD.
Leukemia
December 2024
Institute of Hematology and Center for Hemato-Oncological research (CREO), University of Perugia and Santa Maria della Misericordia Hospital, Perugia, Italy.
The nucleophosmin (NPM1) gene encodes for the most abundant nucleolar protein. Thanks to its property to act as histone chaperone and to shuttle between the nucleus and cytoplasm, the NPM1 protein is involved in multiple cellular function that are here extensively reviewed and include the formation of the nucleolus through liquid-liquid phase separation, regulation of ribosome biogenesis and transport, control of DNA repair and centrosome duplication as well as response to nucleolar stress. NPM1 is mutated in about 30-35% of adult acute myeloid leukemia (AML).
View Article and Find Full Text PDFInt J Mol Sci
December 2024
College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
Ribosomal proteins constitute the principal components of ribosomes, and their functions span a wide spectrum. Recent investigations have unveiled their involvement in oocyte and embryo development, playing a pivotal role in reproductive development. Numerous pieces of evidence indicate that ribosomal proteins participate in the regulation of various cellular activities, including nucleolar stress, oxidative stress, cell proliferation and autophagy.
View Article and Find Full Text PDFInflammopharmacology
December 2024
Translational Research Lab, Srinivas Ramanujan Block, Department of Biotechnology, Faculty of Life Sciences, Jamia Millia Islamia, New Delhi, 110025, India.
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