بررسي تاثير جينجرنون A، بر فسفريلاسيون پروتئين هاي JAK2 و STAT3 در ردهٔ‌ سلولي T-ALL

eva‎luating the effect of Gingerenone A on JAK2-STAT3 signaling pathway in T-ALLcell line.

زيست شناسي سلولي مولكولي و ميكروبيولوژي

Acute Lymphoblastic Leukemia (ALL) is one of the most common malignancies in childhood and the T immunophenotype is associated with negative prognosis. Targeted therapy is a novel treatment approach that aims to reduce the side effects of chemotherapy and increase the efficacy of treatment by identifying and blocking specific active pathways in cancer cells. The aim of this study was to investigate the effect of Gingerenone A, a derivative of ginger, on the JAK2-STAT3 signaling pathway in the CCRF-CEM cell line as a targeted treatment for T-ALL. The selection of this signaling pathway was due to its importance in the growth, survival, invasion, and metastasis of T-ALL. Accordingly, 2.4 × 106 CCRF-CEM cells were treated with concentrations of 10 and 40 µM Gingerenone A dissolved in 0.04M DMSO for 72 hours. The treated cells were collected, and Western blot analysis was performed using primary mouse anti human monoclonal antibodies against P-JAK2 and JAK2 (1:100 dilution), P-STAT3 (1:500 dilution), and STAT3 (1:200 dilution) to eva‎luate the phosphorylation levels of JAK2 and STAT3, respectively. The results of this experiment indicated a reduction in JAK2 phosphorylation following treatment with 10 and 40 µM Gingerenone A compared to the control cells (0.56 ± 0.03 and 0.27 ± 0.03 ODU, respectively) (P<0.001). Additionally, the results showed a decrease in STAT3 protein phosphorylation after treatment with 10 and 40 µM Gingerenone A compared to the control cells (0.83 ± 0.03 and 0.58 ± 0.03 ODU, respectively) (p<0.01, P<0.001). The presented values were compared with non-phosphorylated above-mentioned proteins and beta-actin levels. The present research is the first study to demonstrate the anti-cancer effect of Gingerenone A on the T-ALL cell line with respect to the JAK2-STAT3 signaling pathway. The findings of this study are a positive step towards understanding the pathophysiology of T-ALL and improving therapeutic strategies for this disease.

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