A ferrocene-containing nucleoside analogue targets DNA replication in pancreatic cancer cells

Rana, Marium; Perotti, Alessio; Bisset, Lucy M; Smith, James D.; Lamden, Emma; Khan, Zahra; Ismail, Media K.; Ellis, Katherine; Armstrong, Katie; Hodder, Samantha; Bertoli, Cosetta; Meneguello, Letícia; Bruin, Robertus A.M. de; Morris, Joanna R.; Romero‐Canelón, Isolda; Tucker, James H. R.; Hodges, Nikolas J.

doi:10.1093/mtomcs/mfac041

Cited by 3 publications

(1 citation statement)

References 65 publications

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“…(GEM), classified as an antimetabolite chemotherapy agent, exerts its therapeutic effects primarily by disrupting the synthesis of Deoxyribonucleic Acid (DNA) and Ribonucleic Acid (RNA) within cancer cells. Through the inhibition of cellular division and replication processes, GEM obstructs cancer cell proliferation, thereby curbing tumor growth and spreading [4] . As reported, GEM, in the context of cancer, can transform into active metabolites and upon entry into cancer cells, phosphorylates into GEM diphosphate (dFdCDP).…”

Section: Gemcitabinementioning

confidence: 99%

Mechanistic Study of the Effects of Different Dosages of Gemcitabine on the Migratory and Invasive Abilities of Lung Adenocarcinoma A549 Cells

Wang,

Qiao,

Wang

2024

IJPS

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Lung adenocarcinoma is known to be a malignancy and a leading contributor to mortality. This research intended to delve into the impact of various dosages of gemcitabine on lung adenocarcinoma A549 and PC-9 cells proliferation, migration, and invasion. Additionally, the possible underlying mechanisms were also examined. An in vitro cell model was utilized in the experiment. Varying doses of gemcitabine (2.5, 5, 10 μM) were administered for treating A549 and PC-9 for 0 h-96 h. 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide determined the half-maximal inhibitory concentration of gemcitabine in A549 and PC-9. The experiment of cell counting kit-8 assayed cell proliferation and flow cytometry tracked cell apoptosis. The assay of Transwell examined cell migration and invasion. Furthermore, the analysis of Western blot gauged the profiles of apoptotic proteins c-caspase 3 and B-cell lymphoma 2-associated X protein, the antiapoptotic protein B-cell lymphoma 2, and the Janus tyrosine kinase 2/signal transducer and activator of the transcription 3 signaling pathway in A549 and PC-9. As suggested by our findings, gemcitabine dampened proliferation, invasion, and migration while boosting apoptosis in the cells of A549 and PC-9. Further investigations unveiled that gemcitabine impeded Janus tyrosine kinase 2/signal transducer and activator of the transcription 3 signaling pathway activation in these cells. To conclude, this research has corroborated that gemcitabine exerts inhibitory effects on A549 and PC-9 cells' proliferation, invasion, and migration capabilities by repressing Janus tyrosine kinase 2/signal transducer and activator of the transcription 3 signaling pathway activation under lung adenocarcinoma conditions.

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Section: Gemcitabinementioning

confidence: 99%

Mechanistic Study of the Effects of Different Dosages of Gemcitabine on the Migratory and Invasive Abilities of Lung Adenocarcinoma A549 Cells

Wang,

Qiao,

Wang

2024

IJPS

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Design, Synthesis, and Evaluation of Biological Activity of Ferrocene‐Ispinesib Hybrids: Impact of a Ferrocenyl Group on the Antiproliferative and Kinesin Spindle Protein Inhibitory Activity

Kowalczyk

Błauż

Ayine-Tora

et al. 2023

Chemistry A European J

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With the aim to combine more than one biologically-active component in a single molecule, derivatives of ispinesib and its (S) analogue were prepared that featured ferrocenyl moieties or bulky organic substituents. Inspired by the strong kinesin spindle protein (KSP) inhibitory activity of ispinesib, the compounds were investigated for their antiproliferative activity. Among these compounds, several derivatives demonstrated significantly higher antiproliferative activity than ispinesib with nanomolar IC 50 values against cell lines. Further evaluation indicated that the antiproliferative activity is not directly correlated with their KSP inhibitory activity while docking suggested that several of the derivatives may bind in a manner similar to ispinesib. In order to investigate the mode of action further, cell cycle analysis and reactive oxygen species formation were investigated. The improved antiproliferative activity of the most active compounds may be assigned to synergic effects of various factors such as KSP inhibitory activity due to the ispinesib core and ability to generate ROS and induce mitotic arrest.

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Cascaded Nanozyme Based pH‐Responsive Oxygenation for Targeted Eradication of Resistant Helicobacter Pylori

Tong,

Liu,

et al. 2024

Small

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Nanozymes, as substitutes for natural enzymes, are constructed as cascade catalysis systems for biomedical applications due to their inherent catalytic properties, high stability, tunable physicochemical properties, and environmental responsiveness. Herein, a multifunctional nanozyme is reported to initiate cascade enzymatic reactions specific in acidic environments for resistant Helicobacter pylori (H. pylori) targeting eradication. The cobalt‐coated Prussian blue analog based FPB‐Co‐Ch NPs displays oxidase‐, superoxide dismutase‐, peroxidase‐, and catalase‐ mimicking activities that trigger • and H2O2 to supply O2, thereby killing H. pylori in the stomach. To this end, chitosan is modified on the surface to exert bacterial targeted adhesion and improve the biocompatibility of the composite. In the intestinal environment, the cascade enzymatic activities are significantly inhibited, ensuring the biosafety of the treatment. In vitro, sensitive and resistant strains of H. pylori are cultured and the antibacterial activity is evaluated. In vivo, murine infection models are developed and its success is confirmed by gastric mucosal reculturing, Gram staining, H&E staining, and Giemsa staining. Additionally, the antibacterial capacity, anti‐inflammation, repair effects, and biosafety of FPB‐Co‐Ch NPs are comprehensively investigated. This strategy renders a drug‐free approach that specifically targets and kills H. pylori, restoring the damaged gastric mucosa while relieving inflammation.

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A ferrocene-containing nucleoside analogue targets DNA replication in pancreatic cancer cells

Cited by 3 publications

References 65 publications

Mechanistic Study of the Effects of Different Dosages of Gemcitabine on the Migratory and Invasive Abilities of Lung Adenocarcinoma A549 Cells

Mechanistic Study of the Effects of Different Dosages of Gemcitabine on the Migratory and Invasive Abilities of Lung Adenocarcinoma A549 Cells

Design, Synthesis, and Evaluation of Biological Activity of Ferrocene‐Ispinesib Hybrids: Impact of a Ferrocenyl Group on the Antiproliferative and Kinesin Spindle Protein Inhibitory Activity

Cascaded Nanozyme Based pH‐Responsive Oxygenation for Targeted Eradication of Resistant Helicobacter Pylori

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