A Multi-action Pt(IV)Conjugate with Oleate and Cinnamate Ligands Targets Human Epithelial Growth Factor Receptor HER2 in Aggressive Breast Cancer Cells

0536137 - BFÚ 2021 RIV DE eng J - Journal Article
Kostrhunová, Hana - Zajac, Juraj - Marková, Lenka - Brabec, Viktor - Kašpárková, Jana
A Multi-action Pt(IV)Conjugate with Oleate and Cinnamate Ligands Targets Human Epithelial Growth Factor Receptor HER2 in Aggressive Breast Cancer Cells.
Angewandte Chemie - International Edition. Roč. 59, č. 47 (2020), s. 21157-21162. ISSN 1433-7851. E-ISSN 1521-3773
R&D Projects: GA ČR(CZ) GA18-09502S
Institutional support: RVO:68081707
Keywords : delivery * acid * cisplatin * culture * drug
OECD category: Physical chemistry
Impact factor: 15.336, year: 2020
Method of publishing: Limited access
https://onlinelibrary.wiley.com/doi/10.1002/anie.202009491

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 Pt(IV)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 Pt(II)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 Pt(IV)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.
Permanent Link: http://hdl.handle.net/11104/0313959