Spheroid-based 3D cell cultures identify salinomycin as a promising drug for the treatment of chondrosarcoma

Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society
Francesca PerutN Baldini

Abstract

Chondrosarcoma (CS) is a cartilage malignancy of adulthood that is treated by surgery alone, since chemotherapy is considered ineffective. Unfortunately, a large proportion of patients with CS develop lung metastases, and several die of the disease. In this study, we compared 3D-spheroid cultures and conventional cell monolayer models in order to identify the best way to select anticancer agents that could be effective for the systemic control of CS. Using SW1353 cells, we developed a three-dimensional (3D) in vitro culture model to mimic in vivo features of CS microenvironment and evaluated the efficacy of different drugs to modulate CS cell proliferation and survival in 2D versus 3D-cultures. Doxorubicin (DXR) and cisplatin, that are widely employed in sarcomas, were less effective on 3D-CS spheroids when compared to standard monolayer models, whereas treatment with the ionophore salinomycin (SAL) had a strong cytotoxic effect both on 2D and 3D-cultures. Furthermore, as demonstrated by the reduced viability and the enhanced DXR nuclear localization, SAL enhanced DXR cytotoxicity in 3D-CS spheroids also at sub-lethal doses. SAL activity on 3D-CS spheroids was mediated by a significant induction of apoptosis via caspase activat...Continue Reading

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Citations

Jul 19, 2019·Frontiers in Physiology·Margherita CortiniSofia Avnet
Sep 3, 2020·International Journal of Molecular Sciences·Kamila BiałkowskaKatarzyna Miłowska
Jul 18, 2020·Journal of Hematology & Oncology·Michele ZanoniAnna Tesei
Jan 6, 2019·European Journal of Medicinal Chemistry·Michał Antoszczak
Jan 12, 2021·Frontiers in Molecular Biosciences·Ieva PalubeckaitėJudith V M G Bovée
Aug 29, 2020·Clinical Orthopaedics and Related Research·Terri A Zachos
May 30, 2020·Clinical Orthopaedics and Related Research·Ruichen MaKurt R Weiss
Jul 27, 2021·Journal of Bone Oncology·Javier Munoz-GarciaDominique Heymann
Nov 23, 2021·Toxicology Mechanisms and Methods·Andressa Megumi NiwaMário Sérgio Mantovani

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