Effects of Iron Chelation in Osteosarcoma

• Published in: Current cancer drug targets Vol. 21; no. 5; p. 443
• Main Authors: Argenziano, Maura, Di Paola, Alessandra, Tortora, Chiara, Di Pinto, Daniela, Pota, Elvira, Di Martino, Martina, Perrotta, Silverio, Rossi, Francesca, Punzo, Francesca
• Format: Journal Article
• Language: English
• Published: Netherlands 01-01-2021
• Subjects: Apoptosis - drug effects; Benzoates - pharmacology; Bone Neoplasms - drug therapy; Bone Neoplasms - metabolism; Cell Cycle - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Deferasirox - pharmacology; Drug Therapy, Combination; Humans; Hydrazines - pharmacology; Iron Chelating Agents - pharmacology; Osteosarcoma - drug therapy; Osteosarcoma - metabolism; Pyrazoles - pharmacology; Treatment Outcome; iron chelation; deferasirox; MG63; 143B; Osteosarcoma; eltrombopag
• ISSN: 1873-5576
• DOI: 10.2174/1568009620666201230090531

Osteosarcoma is an aggressive bone tumor. It represents the principal cause of cancer-associated death in children. Considering the recent findings on the role of iron in cancer, iron chelation has been investigated for its antineoplastic properties in many tumors. Deferasirox is the most used iron chelator compound and in previous studies showed an anticancer effect in hematologic and solid malignancies. Eltrombopag is a Thrombopoietin receptor used in thrombocytopenia that also binds and mobilize iron. It demonstrated an effect on iron overload conditions and also in contrasting cancer cell proliferation.
We analyzed the effects of deferasirox and eltrombopag in human osteosarcoma cells in an attempt to identify other therapeutic approaches for this tumor.
We cultured and treated with deferasirox and Eltrombopag, alone and in combination, two human osteosarcoma cell lines, MG63 and 143B. After 72h exposure, we performed RTqPCR, Western Blotting, Iron Assay and cytofluorimetric assays to evaluate the effect on viability, apoptosis, cell cycle progression and ROS production.
The iron-chelating properties of the two compounds are also confirmed in osteosarcoma, but we did not observe any direct effect on tumor progression.
We tested deferasirox and eltrombopag, alone and in combination, in human osteosarcoma cells for the first time and demonstrated that their iron-chelating activity does not influence biochemical pathways related to cancer progression and maintenance.
Although further investigations on possible effects mediated by cells of the tumor microenvironment could be of great interest, in vitro iron chelation in osteosarcoma does not impair tumor progression.