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Contribution of Mitochondrial Activity to Doxorubicin-Resistance in Osteosarcoma Cells.
Giacomini, Isabella; Cortini, Margherita; Tinazzi, Mattia; Baldini, Nicola; Cocetta, Veronica; Ragazzi, Eugenio; Avnet, Sofia; Montopoli, Monica.
Afiliação
  • Giacomini I; Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padova, Italy.
  • Cortini M; Biomedical Science and Technologies and Nanobiotechnology Lab, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy.
  • Tinazzi M; Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padova, Italy.
  • Baldini N; Biomedical Science and Technologies and Nanobiotechnology Lab, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy.
  • Cocetta V; Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy.
  • Ragazzi E; Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padova, Italy.
  • Avnet S; Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padova, Italy.
  • Montopoli M; Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy.
Cancers (Basel) ; 15(5)2023 Feb 21.
Article em En | MEDLINE | ID: mdl-36900165
ABSTRACT
Osteosarcoma is considered the most common bone tumor affecting children and young adults. The standard of care is chemotherapy; however, the onset of drug resistance still jeopardizes osteosarcoma patients, thus making it necessary to conduct a thorough investigation of the possible mechanisms behind this phenomenon. In the last decades, metabolic rewiring of cancer cells has been proposed as a cause of chemotherapy resistance. Our aim was to compare the mitochondrial phenotype of sensitive osteosarcoma cells (HOS and MG-63) versus their clones when continuously exposed to doxorubicin (resistant cells) and identify alterations exploitable for pharmacological approaches to overcome chemotherapy resistance. Compared with sensitive cells, doxorubicin-resistant clones showed sustained viability with less oxygen-dependent metabolisms, and significantly reduced mitochondrial membrane potential, mitochondrial mass, and ROS production. In addition, we found reduced expression of TFAM gene generally associated with mitochondrial biogenesis. Finally, combined treatment of resistant osteosarcoma cells with doxorubicin and quercetin, a known inducer of mitochondrial biogenesis, re-sensitizes the doxorubicin effect in resistant cells. Despite further investigations being needed, these results pave the way for the use of mitochondrial inducers as a promising strategy to re-sensitize doxorubicin cytotoxicity in patients who do not respond to therapy or reduce doxorubicin side effects.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article