Resveratrol reduces the presence of Extracellular Traps (ETs) in acute promyelocytic leukemia (NB4) cells

NETosis and ETosis are processes involving the release of extracellular traps (ETs). They have been linked to cancer progression, particularly in promoting metastasis and tumor-associated thrombosis. This indicates that redundant NETs/ETs formation can contribute to cancer spread, making it a potential therapeutic target. Therefore, discovering ways to inhibit NETs/ETs formation could improve treatment outcomes.

The ETOsis phenomenon in Human acute promyelocytic leukemia may lead to activating the platelets and coagulation factors. Accordingly, coagulation and fibrinolysis can be promoted. Resveratrol (RSV) is a botanical antioxidant with anti-inflammatory and anti-leukemia effects.

This study was conducted to assess the inhibitory effect of RSV on the occurrence of ETOsis in the NB4 cell line.

Methods: Human acute promyelocytic leukemia cell line (NB4) was stimulated and treated by lipo-polysaccharides (LPS) and RSV, respectively. Sytox green and a fluorescent microscope were used to assess the ETOsis in NB4 cells. Furthermore, the expression level of peptidylarginine deiminase 4 (PAD4) gene and the occurrence of ETOsis in NB4 cells were evaluated by real-time PCR and flow cytometry, respectively. Moreover, an enzyme-linked immunosorbent assay (ELISA) kit was utilized to measure tumor necrosis factor-α (TNF-α) cytokine.

Results: Following treatment with RSV, a significant decrease in PAD4 gene expression and TNF-α cytokine concentration in the supernatant of NB4 cell line culture medium was observed. Besides, ETOsis in the NB4 cells treated with LPS and RSV decreased.

Conclusion: The findings demonstrated that RSV can inhibit ETOsis in NB4 cells. By inhibiting ETOsis, RSV may reduce bleeding and, consequently, failure after treatment in acute promyelocytic leukemia (APL) patients.

Dr. Minoo Shahidi is an Immunohematologist specializing in cancer, angiogenesis and NETosis research. She holds a PhD in Immunohematology from Surrey University, UK. Dr. Shahidi has published extensively on Hematologic Malignancies and Inflammation. She is currently Associate Professor at Department of Hematology and Blood Banking School of Allied Medical & Sciences and Pediatric Growth and Development Research Center Endocrinology & Metabolism Research Institute, Iran University of Medical Sciences, Tehran, Iran.