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J Phys Chem B ; 123(32): 6968-6979, 2019 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-31339317

RESUMEN

This study aimed at the development of improved drugs against human osteosarcoma, which is the most common primary bone tumor in children and teenagers with a low prognosis. New insights into the impact of an unconventional Pd(II) anticancer agent on human osteosarcoma cells were obtained by synchrotron radiation-Fourier transform infrared microspectroscopy and quasi-elastic neutron scattering (QENS) experiments from its effect on the cellular metabolism to its influence on intracellular water, which can be regarded as a potential secondary pharmacological target. Specific infrared biomarkers of drug action were identified, enabling a molecular-level description of variations in cellular biochemistry upon drug exposure. The main changes were detected in the protein and lipid cellular components, namely, in the ratio of unsaturated-to-saturated fatty acids. QENS revealed reduced water mobility within the cytoplasm for drug-treated cells, coupled to a disruption of the hydration layers of biomolecules. Additionally, the chemical and dynamical profiles of osteosarcoma cells were compared to those of metastatic breast cancer cells, revealing distinct dissimilarities that may influence drug activity.


Asunto(s)
Antineoplásicos/farmacología , Ácidos Grasos/metabolismo , Difracción de Neutrones , Osteosarcoma/tratamiento farmacológico , Paladio/farmacología , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Sincrotrones/instrumentación , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Cisplatino/farmacología , Femenino , Humanos , Osteosarcoma/metabolismo , Osteosarcoma/patología , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Células Tumorales Cultivadas
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