ArticleInternational journal of molecular sciences2018
Etoposide-Induced Apoptosis in Cancer Cells Can Be Reinforced by an Uncoupled Link between Hsp70 and Caspase-3.
Article in International journal of molecular sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 26 citations in OpenAlex.
- Molecular mechanism of Saikosaponin-d in the treatment of gastric cancer based on network pharmacology and in vitro experimental verification.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Hsp70 Negatively Regulates Autophagy via Governing AMPK Activation, and Dual Hsp70-Autophagy Inhibition Induces Synergetic Cell Death in NSCLC Cells.International journal of molecular sciences · 2024Article
- HSP70 Family in Cancer: Signaling Mechanisms and Therapeutic Advances.Biomolecules · 2023Review
- Extracellular Polysaccharide fromJournal of clinical and translational hepatology · 2022Article
- Article
- Quantifying Cytosolic Cytochrome c Concentration Using Carbon Quantum Dots as a Powerful Method for Apoptosis Detection.Pharmaceutics · 2021Article
- Inducing regulated necrosis and shifting macrophage polarization with anti-EMMPRIN antibody (161-pAb) and complement factors.Journal of leukocyte biology · 2021Article
- Ethanol Enhances Hyperthermia-Induced Cell Death in Human Leukemia Cells.International journal of molecular sciences · 2021Article
- Significant reductions in apoptosis-related proteins (HSPA6, HSPA8, ITGB3, YWHAH, and PRDX6) are involved in immune thrombocytopenia.Journal of thrombosis and thrombolysis · 2021Article
- Delivery of functional exogenous proteins by plant-derived vesicles to human cells in vitro.Scientific reports · 2021Article
- Bcl-2 Associated Athanogene 2 (BAG2) is Associated With Progression and Prognosis of Hepatocellular Carcinoma: A Bioinformatics-Based Analysis.Pathology oncology research : POR · 2021Article
- β-elemene promotes the senescence of glioma cells through regulating YAP-CDK6 signaling.American journal of cancer research · 2021Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Hsp70 chaperone binds and inhibits proteins implicated in apoptotic signaling including Caspase-3. Induction of apoptosis is an important mechanism of anti-cancer drugs, therefore Hsp70 can act as a protective system in tumor cells against therapeutic agents. In this study we present an assessment of candidate compounds that are able to dissociate the complex of Hsp70 with Caspase-3, and thus sensitize cells to drug-induced apoptosis. Using the PASS program for prediction of biological activity we selected a derivative of benzodioxol (BT44) that is known to affect molecular chaperones and caspases. Drug affinity responsive target stability and microscale thermophoresis assays indicated that BT44 bound to Hsp70 and reduced the chaperone activity. When etoposide was administered, heat shock accompanied with an accumulation of Hsp70 led to an inhibition of etoposide-induced apoptosis. The number of apoptotic cells increased following BT44 administration, and forced Caspase-3 processing. Competitive protein⁻protein interaction and immunoprecipitation assays showed that BT44 caused dissociation of the Hsp70⁻Caspase-3 complex, thus augmenting the anti-tumor activity of etoposide and highlighting the potential role of molecular separators in cancer therapy.
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