Potential Cytoprotective and Anti-Apoptotic Effect of Metamizole Alone and in Combination with Cytostatic Drugs Observed In Vitro in Canine (D-17) and Human (U-2 OS) Osteosarcoma Cell Lines.

Abstract

Metamizole (dipyrone) is still a frequently used drug in human and veterinary medicine, especially for pain relief, sometimes also in osteosarcoma treatment. It has a very strong analgesic and antipyretic effect and weaker anti-inflammatory activity. Additionally, it has spasmolytic properties. It is used in many species, including dogs, cats, pigs, cattle, horses, and humans, in Europe, Canada, and South America. The aim of this study was to assess a potential synergism of metamizole as a non-steroidal anti-inflammatory drug with routinely used cytostatics (cisplatin, carboplatin, doxorubicin, and etoposide). In vitro studies were performed on a canine osteosarcoma D-17 cell line and a human U-2 OS cell line. We used the MTT method to assess cell viability, TUNEL staining to assess proapoptotic effects, and propidium iodide to analyse the cell cycle (potential arrest). The obtained results showed that metamizole at 50 μg/mL has potential cytoprotective and anti-apoptotic effects. Metamizole administered simultaneously with cytostatic drugs reduced their cytotoxic effect, which may suggest that such a combination of drugs used in the treatment of osteosarcoma may significantly reduce therapy effectiveness.