Cold atmospheric plasma enhances doxorubicin selectivity in metastasic bone cancer

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 i...

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Detalles Bibliográficos
Autores: Mateu Sanz, Miguel|||0000-0001-5117-6071, Ginebra Molins, Maria Pau|||0000-0002-4700-5621, Tornin Cavielles, Juan|||0000-0002-7676-3958, Canal Barnils, Cristina|||0000-0002-3039-7462
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universitat Politècnica de Catalunya (UPC)
Repositorio:UPCommons. Portal del coneixement obert de la UPC
Idioma:inglés
OAI Identifier:oai:upcommons.upc.edu:2117/372865
Acceso en línea:https://hdl.handle.net/2117/372865
https://dx.doi.org/10.1016/j.freeradbiomed.2022.07.007
Access Level:acceso abierto
Palabra clave:Bone regeneration
Cold atmospheric plasmas
Plasma conditioned liquids
Prostate cancer
Bone metastasis
Doxorubicin
Ossos
Àrees temàtiques de la UPC::Enginyeria biomèdica::Biomaterials
Descripción
Sumario: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 combination 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.