Metamizole Reduces The Expression of OCT4, SOX2, SOX4 in Hematopoietic Stem/Progenitor Cells Directed to Differentiation in In Vitro Hematopoiesis Simulation

Erkan Maytalman; Dilara Nemutlu Samur

Makale detayları

Metamizole Reduces The Expression of OCT4, SOX2, SOX4 in Hematopoietic Stem/Progenitor Cells Directed to Differentiation in In Vitro Hematopoiesis Simulation

Yazarlar:

Erkan Maytalman | Dilara Nemutlu Samur

Yayıncı:

Alanya Alaaddin Keykubat Üniversitesi

Ana Başlıklar:

Klinik Tıp Bilimleri (Diğer)

Dergi:

Acta Medica Alanya Vol.9 Issue 2, pp.99-107

Belge Tipi:

Makale

Yayın Tarihi:

3/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001356111

pISSN:

2587-0319

Anahtar kelimeler:

Özet:

 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 50.967.60 µM and the highest value was 165.518.21 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 stemprogenitor 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.

 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 50.967.60 µM and the highest value was 165.518.21 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 stemprogenitor 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.

 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 50.967.60 µM and the highest value was 165.518.21 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 stemprogenitor 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.

 Amaç: Metamizol analjezik ve antipiretik etkisi nedeniyle kullanılan bir non-steroidal antiinflamatuvar ilaçtır. Agranülositoz bu ilacın bazı ülkelerde kullanımını sınırlayan önemli bir yan tesiridir fakat bu yan tesirin olası mekanizmalarıyla kanser hücrelerinde apoptozu teşvik ettiği de gösterilmiştir. Bu etkilerin altında yatan mekanizmalar yeterince açıklanmamıştır. Yöntem: Çalışmada sağlıklı allojeneik kök hücre donörlerinden toplanan kök hücre ürün örneklerinden elde edilen hücreler kullanıldı. Metamizolün hücreler üzerindeki proliferatif-sitotoksik etkilerinin analizi için MTT testi uygulandı. Ayrıca farklılaşmanın ve OCT4, SOX2, SOX4ün ekspresyon analizleri için CFU-Mix kültürü yapıldı. Transkripsiyon faktörlerinin ekspresyon katsayıları RT-qPCR ile tespit edildi. Bulgular: Metamizol 10 µM başlayarak artan konsantrasyonlarda hücrelerin çoğalmasını sınırlandırdı. Metamizolün IC50 değerleri örnekler arasında belirgin derecede farklıydı. IC50 için en düşük değer 50,967,60 µM en yüksek 165,518,21 µM olarak elde edildi. Granulosit-makrofaj koloni sayımlarında ve OCT4, SOX4 mRNA ekspresyonlarında 10 ve 100 µM konsantrasyonlarda azalma oldu. SOX2 için azalma 100 µM konsantrasyonda gerçekleşti. Sonuç: Sonuçlarımız metamizolün transkripsiyon faktörleri üzerinden hematopoetik kökprogenitör hücrelerin proliferasyon ve farklılaşmasını sınırlandırabileceğini ve olası agranülositoz olgularında bu etkinin de sorumlu olabileceğini işaret etti. NSAIlerin kanser hücreleri üzerine de apoptotik etkileri de gösterilmiştir. Hücrelerin gelişmesi ve farklılaşmasında önemli rolleri olan transkripsiyon faktörlerinin ekspresyonunu sınırlandırabilmesi, bu ilacın antineoplastik ilaçlarla sinerjik etki için birlikte kullanımlarının önünü açabilir.

Makale detayları

Metamizole Reduces The Expression of OCT4, SOX2, SOX4 in Hematopoietic Stem/Progenitor Cells Directed to Differentiation in In Vitro Hematopoiesis Simulation

Yazarlar:

Erkan Maytalman | Dilara Nemutlu Samur

Yayıncı:

Alanya Alaaddin Keykubat Üniversitesi

Ana Başlıklar:

Klinik Tıp Bilimleri (Diğer)

Dergi:

Acta Medica Alanya Vol.9 Issue 2, pp.99-107

Belge Tipi:

Makale

Yayın Tarihi:

3/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001356111

pISSN:

2587-0319

Metamizole

NSAID

Hematopoesis

OCT4

SOX2

SOX4Metamizol

NSAİİ

Hematopoez

OCT4

SOX2

SOX4

Sayı

Makale detayları

Yazarlar: Erkan Maytalman | Dilara Nemutlu Samur

Yayıncı: Alanya Alaaddin Keykubat Üniversitesi

Ana Başlıklar: Klinik Tıp Bilimleri (Diğer)

Dergi: Acta Medica Alanya Vol.9 Issue 2, pp.99-107

Belge Tipi: Makale

Yayın Tarihi: 3/2025

Belge Dili: İngilizce

Document ID (Org No.): 2001356111

pISSN: 2587-0319

Sayı

Yazarlar:

Erkan Maytalman | Dilara Nemutlu Samur

Yayıncı:

Alanya Alaaddin Keykubat Üniversitesi

Ana Başlıklar:

Klinik Tıp Bilimleri (Diğer)

Dergi:

Acta Medica Alanya Vol.9 Issue 2, pp.99-107

Belge Tipi:

Makale

Yayın Tarihi:

3/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001356111

pISSN:

2587-0319