ArticleCell death & disease2017
Protein kinase A activation by the anti-cancer drugs ABT-737 and thymoquinone is caspase-3-dependent and correlates with platelet inhibition and apoptosis.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- Article
- Light-gated integrator for highlighting kinase activity in living cells.Nature communications · 2024Article
- Antiplatelet Effects of Flavonoid Aglycones Are Mediated by Activation of Cyclic Nucleotide-Dependent Protein Kinases.International journal of molecular sciences · 2024Article
- Light-gated Integrator for Highlighting Kinase Activity in Living Cells.bioRxiv : the preprint server for biology · 2024Article
- Inhibition of GPIb-α-mediated apoptosis signaling enables cold storage of platelets.Haematologica · 2023Article
- Review
- Review
- Review
- Mechanisms Underlying Dichotomous Procoagulant COAT Platelet Generation-A Conceptual Review Summarizing Current Knowledge.International journal of molecular sciences · 2022Review
- Curcumin at Low Doses Potentiates and at High Doses Inhibits ABT-737-Induced Platelet Apoptosis.International journal of molecular sciences · 2021Article
- Nutritional Value and Preventive Role ofMolecules (Basel, Switzerland) · 2021Review
- Sulforaphane induces S-phase arrest and apoptosis via p53-dependent manner in gastric cancer cells.Scientific reports · 2021Article
- Effects of bacterial lipopolysaccharides on platelet function: inhibition of weak platelet activation.Scientific reports · 2020Article
- Metformin as Potential Therapy for High-Grade Glioma.Cancers · 2020Article
- Effect of metformin on cell proliferation, apoptosis, migration and invasion in A172 glioma cells and its mechanisms.Molecular medicine reports · 2019Article
- Regional methylome profiling reveals dynamic epigenetic heterogeneity and convergent hypomethylation of stem cell quiescence-associated genes in breast cancer following neoadjuvant chemotherapy.Cell & bioscience · 2019Article
- Pretreatment albumin globulin ratio has a superior prognostic value in laryngeal squamous cell carcinoma patients: a comparison study.Journal of Cancer · 2019Article
Corrections and comments
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Authors and funding
8 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemotherapy-induced thrombocytopenia is a common bleeding risk in cancer patients and limits chemotherapy dose and frequency. Recent data from mouse and human platelets revealed that activation of protein kinase A/G (PKA/PKG) not only inhibited thrombin/convulxin-induced platelet activation but also prevented the platelet pro-coagulant state. Here we investigated whether or not PKA/PKG activation could attenuate caspase-dependent apoptosis induced by the anti-cancer drugs ABT-737 (the precursor of navitoclax) and thymoquinone (TQ), thereby potentially limiting chemotherapy-induced thrombocytopenia. This is particularly relevant as activation of cyclic nucleotide signalling in combination chemotherapy is an emerging strategy in cancer treatment. However, PKA/PKG-activation, as monitored by phosphorylation of Vasodilator-stimulated phosphoprotein (VASP), did not block caspase-3-dependent platelet apoptosis induced by the compounds. In contrast, both substances induced PKA activation themselves and PKA activation correlated with platelet inhibition and apoptosis. Surprisingly, ABT-737- and TQ-induced VASP-phosphorylation was independent of cAMP levels and neither cyclases nor phosphatases were affected by the drugs. In contrast, however, ABT-737- and TQ-induced PKA activation was blocked by caspase-3 inhibitors. In conclusion, we show that ABT-737 and TQ activate PKA in a caspase-3-dependent manner, which correlates with platelet inhibition and apoptosis and therefore potentially contributes to the bleeding risk in chemotherapy patients.
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