Translation inhibition and suppression of stress granules formation by cisplatin

Pietras, Paulina; Aulas, Anaïs; Fay, Marta M.; Leśniczak-Staszak, Marta; Sowiński, Mateusz; Lyons, Shawn M.; Szaflarski, Witold; Ivanov, Pavel

doi:10.1016/j.biopha.2021.112382

Cited by 19 publications

(9 citation statements)

References 38 publications

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“…Nonetheless, the enrichment of the translation process supports earlier research that proves cisplatin does not just target DNA but also affects cellular translation, which can subsequently cause polysomes to disassemble and aggregate ribosomal subunits [ 55 ]. This is because cisplatin can specifically target a number of ribosomal functional centers, indicating potential strategies by which cisplatin could hinder protein synthesis [ 56 ].…”

Section: Discussionsupporting

confidence: 77%

Proteomic and metabolomic signatures of U87 glioblastoma cells treated with cisplatin and/or paclitaxel

Ahmed,

Semreen,

Giddey

et al. 2023

Annals of Medicine

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Background Glioblastoma (GBM) is a primary malignancy of the central nervous system and is classified as a grade IV astrocytoma by the World Health Organization (WHO). Although GBM rarely metastasizes, its prognosis remains poor. Moreover, the standard treatment for GBM, temozolomide (TMZ), is associated with chemoresistance, which is a major factor behind GBM-related deaths. Investigating drugs with repurposing potential in the context of GBM is worthwhile to bypass lengthy bench-to-bedside research. The field of omics has garnered significant interest in scientific research because of its potential to delineate the intricate regulatory network underlying tumor development. In particular, proteomic and metabolomic analyses are powerful approaches for the investigation of metabolic enzymes and intermediate metabolites since they represent the functional end of the cancer phenotype. Methods We chose two of the most widely prescribed anticancer drugs, cisplatin and paclitaxel. To our knowledge, the current literature lacks studies examining their effects on metabolic and proteomic alterations in GBM. We employed the mass spectrometry technological platform ‘UHPLC-Q-TOF-MS/MS’ to examine the changes in the proteome and metabolome profiles of the U87 cell line with defined concentrations of cisplatin and/or paclitaxel via an untargeted approach. Results A total of 1,419 distinct proteins and 90 metabolites were generated, and subsequent analysis was performed. We observed that upon treatment with cisplatin (9.5 μM), U87 cells exhibited apparent efforts to cope with this exogenous stressor, understanding the effect of paclitaxel (5.3 μM) on altering the transport machinery of the cell, and how the combination of cisplatin and/or paclitaxel suggests potential interactions with promising benefits in GBM therapeutics. Conclusion Our research provides a detailed map of alterations in response to cisplatin and paclitaxel treatment, provides crucial insights into the molecular basis of their action, and paves the way for further research to identify molecular targets for this elusive malignancy.

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Section: Discussionsupporting

confidence: 77%

Proteomic and metabolomic signatures of U87 glioblastoma cells treated with cisplatin and/or paclitaxel

Ahmed,

Semreen,

Giddey

et al. 2023

Annals of Medicine

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“…SGs formation is relevant to stress-induced resistance to cancer chemotherapy, suppressing cancer cell apoptosis by inhibiting the MAPK pathway during environmental stress [ 68 ]. However, cisplatin disrupts SGs formation and causes cancer cell apoptosis by inducing ribosomal subunit aggregation [ 69 ].…”

Section: Stress Granulesmentioning

confidence: 99%

Diverse roles of biomolecular condensation in eukaryotic translational regulation

Zhang,

Kang,

Liu

et al. 2023

RNA Biology

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Biomolecular condensates, forming membrane-less organelles, orchestrate the sub-cellular compartment to execute designated biological processes. An increasing body of evidence demonstrates the involvement of these biomolecular condensates in translational regulation. This review summarizes recent discoveries concerning biomolecular condensates associated with translational regulation, including their composition, assembly, and functions. Furthermore, we discussed the common features among these biomolecular condensates and the critical questions in the translational regulation areas. These emerging discoveries shed light on the enigmatic translational machinery, refine our understanding of translational regulation, and put forth potential therapeutic targets for diseases born out of translation dysregulation.

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“…Notably, these SGs rapidly disassemble when stress is relieved. They generally contain RNAs, RBPs, and 40S ribosomal subunits and comprise cell-type-or stress-specific components [9]; however, SGs strictly require translation machinery and they are disrupted by translation inhibitors [10].…”

Section: Sgsmentioning

confidence: 99%

Regulation of Cellular Ribonucleoprotein Granules: From Assembly to Degradation via Post-translational Modification

Jeon

Ham

Park

et al. 2022

Cells

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Cells possess membraneless ribonucleoprotein (RNP) granules, including stress granules, processing bodies, Cajal bodies, or paraspeckles, that play physiological or pathological roles. RNP granules contain RNA and numerous RNA-binding proteins, transiently formed through the liquid–liquid phase separation. The assembly or disassembly of numerous RNP granules is strongly controlled to maintain their homeostasis and perform their cellular functions properly. Normal RNA granules are reversibly assembled, whereas abnormal RNP granules accumulate and associate with various neurodegenerative diseases. This review summarizes current studies on the physiological or pathological roles of post-translational modifications of various cellular RNP granules and discusses the therapeutic methods in curing diseases related to abnormal RNP granules by autophagy.

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Translation inhibition and suppression of stress granules formation by cisplatin

Cited by 19 publications

References 38 publications

Proteomic and metabolomic signatures of U87 glioblastoma cells treated with cisplatin and/or paclitaxel

Proteomic and metabolomic signatures of U87 glioblastoma cells treated with cisplatin and/or paclitaxel

Diverse roles of biomolecular condensation in eukaryotic translational regulation

Regulation of Cellular Ribonucleoprotein Granules: From Assembly to Degradation via Post-translational Modification

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