Metamizol İn Vitro Hematopoez Simülasyonunda Farklılaşmaya Yönlendirilen Hematopoetik Kök/Progenitör Hücrelerin OCT4, SOX2, SOX4 Ekspresyonunu Azaltır

Aim: Metamizole is a non-steroidal anti-inflammatory drug used for its analgesic and antipyretic effects. Metamizole-associated agranulocytosis is a significant adverse effect limiting its use in some countries, but it has also been shown to promote apoptosis in cancer cells with possible mechanisms underlying this adverse effect. The mechanisms underlying these effects have not been sufficiently elucidated.Methods: The cells obtained from stem cell product samples collected from healthy allogeneic stem cell donors were used in the study. MTT assay was used to analyse the proliferative-cytotoxic effects of metamizole on cells. CFU-Mix culture was also performed for cell differentiation to granulocyte and analysis of expression of OCT4, SOX2, SOX4. The expression fold change of transcription factors was determined by RT-qPCR.Results: Metamizole limited the proliferation of cells at increasing concentrations starting at 10 µM. The IC50 values of metamizole were significantly different between the samples. The lowest value for IC50 was 50.96±7.60 µM and the highest value was 165.5±18.21 µM. Granulocyte-macrophage colony counts and OCT4, SOX4 mRNA expressions decreased at metamizole concentrations of 10 and 100 µM. For SOX2, the decrease occurred at a concentration of 100 µM.Conclusion: Our results indicated that metamizole may limit the proliferation and differentiation of hematopoietic stem/progenitor cells via transcription factors and this effect may be responsible for possible agranulocytosis cases. NSAIDs have also been shown to have apoptotic effects on cancer cells. The ability to limit the expression of transcription factors that play important roles in cell development and differentiation may pave the way for the synergistic use of this drug with antineoplastic drugs.