Cold atmospheric plasma enhances doxorubicin selectivity in metastasic bone cancer
Por:
Mateu-Sanz, Miguel, Ginebra MP, Tornin-Cavielles J and Canal-Barnils C
Publicada:
1 ago 2022
Ahead of Print:
1 jul 2022
Resumen:
High-dose systemic chemotherapy constitutes a main strategy in the management of bone metastases, employing drugs like doxorubicin (DOX), related with severe side effects. To solve this issue, Cold Atmospheric Plasmas (CAP) have been proposed as potential non-invasive anti-cancer agents capable of improving the efficacy of traditional drugs. Here, we investigate the cytotoxic effects of Plasma Conditioned Medium (PCM) in combi-nation with DOX in prostate cancer cells from bone metastases (PC-3) as well as in non-malignant bone-cells. PCM was able to enhance the cytotoxic potential of DOX both in monolayer and in a 3D bioengineered model mimicking the bone matrix. The combined treatment of PCM + DOX resulted in a profound downregulation of the redox defenses (CAT1, SOD2, GPX1) and drug resistance genes (MRP1, MDR1, BCRP1), resulting in an enhanced uptake of DOX coupled to an overload of intracellular ROS. Besides, PCM improved the cytotoxic potential of DOX interfering on the migratory and clonogenic potential of PC-3 cells. Importantly, non-malignant bone cells were unaffected by the combination of PCM + DOX. Overall, these new findings may represent a new therapeutic approach for the management of bone metastatic prostate cancer in the future.
Filiaciones:
Mateu-Sanz, Miguel:
Biomaterials, Biomechanics and Tissue Engineering Group, Materials Science and Engineering Department, and Research Center for Biomedical Engineering, Universitat Politècnica de Catalunya (UPC), Escola d'Enginyeria Barcelona Est (EEBE), c/Eduard Maristany 14, 08019, Barcelona, Spain
Barcelona Research Center in Multiscale Science and Engineering, UPC, 08019, Barcelona, Spain
Institut de Recerca Sant Joan de Déu, 08034, Barcelona, Spain
Ginebra MP:
Biomaterials, Biomechanics and Tissue Engineering Group, Materials Science and Engineering Department, and Research Center for Biomedical Engineering, Universitat Politècnica de Catalunya (UPC), Escola d'Enginyeria Barcelona Est (EEBE), c/Eduard Maristany 14, 08019, Barcelona, Spain
Barcelona Research Center in Multiscale Science and Engineering, UPC, 08019, Barcelona, Spain
Institut de Recerca Sant Joan de Déu, 08034, Barcelona, Spain
Tornin-Cavielles J:
Biomaterials, Biomechanics and Tissue Engineering Group, Materials Science and Engineering Department, and Research Center for Biomedical Engineering, Universitat Politècnica de Catalunya (UPC), Escola d'Enginyeria Barcelona Est (EEBE), c/Eduard Maristany 14, 08019, Barcelona, Spain
Barcelona Research Center in Multiscale Science and Engineering, UPC, 08019, Barcelona, Spain
Institut de Recerca Sant Joan de Déu, 08034, Barcelona, Spain
Sarcomas and Experimental Therapeutics Laboratory, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, Avenida de Roma, s/n, 33011, Oviedo, Spain
Instituto Universitario de Oncología del Principado de Asturias, 33011, Oviedo, Spain
Canal-Barnils C:
Biomaterials, Biomechanics and Tissue Engineering Group, Materials Science and Engineering Department, and Research Center for Biomedical Engineering, Universitat Politècnica de Catalunya (UPC), Escola d'Enginyeria Barcelona Est (EEBE), c/Eduard Maristany 14, 08019, Barcelona, Spain
Barcelona Research Center in Multiscale Science and Engineering, UPC, 08019, Barcelona, Spain
Institut de Recerca Sant Joan de Déu, 08034, Barcelona, Spain
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