A Multi‐action Pt IV Conjugate with Oleate and Cinnamate Ligands Targets Human Epithelial Growth Factor Receptor HER2 in Aggressive Breast Cancer Cells
Autor: | Hana Kostrhunova, Jana Kasparkova, Lenka Markova, Juraj Zajac, Viktor Brabec |
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Rok vydání: | 2020 |
Předmět: |
chemistry.chemical_classification
Metals in medicine 010405 organic chemistry Peptide General Medicine General Chemistry Prodrug 010402 general chemistry medicine.disease 01 natural sciences Catalysis 0104 chemical sciences Breast cancer Growth factor receptor chemistry Cancer stem cell Cancer cell Cancer research medicine skin and connective tissue diseases Conjugate |
Zdroj: | Angewandte Chemie International Edition. 59:21157-21162 |
ISSN: | 1521-3773 1433-7851 |
Popis: | HER2-positive breast cancer is an aggressive subtype that typically responds poorly to standard chemotherapy. To design an anticancer drug selective for HER2-expressing breast cancer, a PtIV prodrug with axial oleate and cinnamate ligands was synthesized. We demonstrate its superior antiproliferative activity in monolayer and 3D spheroid models; the antiproliferative efficiency increases gradually with increasing expression of HER2. The results also suggest that the released PtII compound inhibits the proliferation of cancer cells by a DNA-damage-mediated mechanism. Simultaneously, the released oleic and cinnamic acid can effectively inhibit HER2 expression. To our knowledge, this is the first platinum-based complex inhibiting HER2 expression that does not contain protein or peptide. Moreover, this PtIV prodrug is capable of overcoming the resistance of cancer stem cells (CSCs), inducing death in both CSCs and differentiated cancer cells. Thus, the results substantiate our design strategy and demonstrate the potential of this approach for the development of new, therapeutically relevant compounds. |
Databáze: | OpenAIRE |
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