Synergistic Growth Inhibitory Effect of Hydroxyurea and SRJ23 Combination on T-ALL Jurkat Cells

Laith Marashdeh¹, Johnson Stanslas¹, Thilakavathy Karuppiah^2,3, Bahariah Khalid^1,*

Abstract

Introduction: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive haematologic neoplasm that accounts for about 15% and 25% of children and adults, respectively of all types of acute lymphoblastic leukemia. Treatment has not shown positive curative sustenance and is cost-effective. SRJ23, a bicyclic lactone, is a novel semi-synthetic derivative of andrographolide while hydroxyurea (HU) is a known inexpensive anticancer agent causing suppression of DNA synthesis by inhibiting ribonucleoside diphosphate reductase and inhibits GDP-GTP exchange to induce apoptosis. We aim to evaluate the inhibitory effect of HU in combination with SRJ23 on the Jurkat cell line and determine its efficacy. Methods: T-ALL (Jurkat cells) were seeded and treated with different concentrations of SRJ23 (0.1, 1, 10, 100 µM) and HU (7.8, 15.6, 31.25, 62.5, 125, 250, 500, and 1000 μM). After 96 hours of incubation, the MTT assay was used to assess the in vitro growth inhibition of the combination towards the cells. An apoptosis assay was also performed by flow cytometry technique using Annexin V-FITC and Propidium Iodide (PI) double staining assay. Result: The dose-response curves showed a reduction of cell viability with a synergistic effect with a combination of concentration of 10 µM SRJ23 with 25 µM HU (combination index of 0.53) or 250 µM HU (combination index of 0.40). The combination induced enhanced apoptosis when compared with single-agent alone. Conclusion: The combination of HU and SRJ23 had a remarkable synergistic effect inhibiting T-ALL Jurkat cells by inducing apoptosis. The combination needs to be tested further both in vitro and in vivo in order to assess how well it works as a potential novel targeted therapy.

Keywords: T-ALL, SRJ23, Hydroxyurea, Synergistic effect, MTT, Apoptosis

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