Sodyum ortovanadat toksisitesinin K562 hücrelerindeki temel aracıları TRAIL-R2 ve Abl'dir

Bahşi P., Polat Ş. N., Dağdeen D. N., Hapil Zevkliler F. Z.

The 49th FEBS CONGRESS, İstanbul, Türkiye, 5 - 09 Temmuz 2025, cilt.15, ss.1, (Özet Bildiri)

  • Yayın Türü: Bildiri / Özet Bildiri
  • Cilt numarası: 15
  • Basıldığı Şehir: İstanbul
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.1
  • Akdeniz Üniversitesi Adresli: Evet

Özet

Sodium orthovanadate (Na3VO4 ) is a potent phosphatase inhibitor with recognized cytotoxic effects, but its precise mechanisms remain to be fully elucidated. In this study, we investigated Na3VO4 ­induced toxicity in K562 chronic myeloid leukemia cells and identified critical molecular mediators.


Treatment of K562 cells with Na3VO4 (100 μM, 72 hours) reduced proliferation by approximately 70% as measured by the alamarBlue (resazurin) assay. Co­ treatment with TRAIL or imatinib further enhanced cytotoxicity, reducing viable cells to 10% and 5%, respectively. To investigate the role of TRAIL­R2, we generated TRAIL­R2 knockout K562 cells by CRISPR­Cas9 plasmid transfection using Turbofect. In these knockout cells, Na3VO4 toxicity was significantly reduced with only ~35% reduction in proliferation. Strikingly, co­treatment with imatinib (Abl inhibitor) completely rescued TRAIL­R2­deficient cells from Na3VO4 ­induced toxicity and restored proliferation to control levels. 

 

Our results demonstrate that TRAIL­R2 and ABL are key mediators of Na3VO4 cytotoxicity in K562 cells. This suggests that the toxic effects of sodium orthovanadate are driven by pathways involving death receptor signaling and ABL kinase activity. These findings provide mechanistic insight into the toxicity of vanadium compounds and point to potential strategies for modulating their effects in leukemia therapy and potentially in other settings where vanadium compounds are used.