Anticancer evaluation of SRJ23 and hydroxyurea treatment combination in T-cell acute lymphoblastic leukaemia cell line

T-cell acute lymphoblastic leukaemia (T-cell ALL) is a hostile haematologic malignancy resulting from the malignant transformation of immature T-cell progenitors. This cancer constitutes approximately 15% of cases in children and 25% in adults. Addressing this heinous disease requires high-dose chemotherapy regimens that enhance survival rates; however, treatment options remain scarce for patients who relapse or exhibit refractory disease, posing a significant challenge. Recent advances in molecular and genetic research have enabled a more precise identification of the underlying causes of T-cell ALL, including genetic mutations, disruptions in cellular pathways, and chromosomal abnormalities associated with this and other haematologic malignancies. This has deepened our understanding of cellular mechanisms and related pathways, allowing for a more targeted selection of combination chemotherapy drugs to achieve optimal outcomes. In the current study, a targeted compound inhibitor (SRJ23) was combined with an antimetabolite clinical agent (Hydroxyurea) to reduce the viability of Jurkat cells and induce apoptosis. Problem statement: SRJ23 exhibits potential for addressing breast, colon, and prostate cancer cell lines, providing insights into the mechanisms involving cell cycle arrest and apoptosis. However, its effects on T-cell acute lymphoblastic leukaemia (V) remain unexplored. While HU proves effective in treating different cancers, its application to T-cell ALL lacks clarity, emphasising the need for a thorough understanding of its mechanisms across diverse medical scenarios. Objective: Aim to evaluate the inhibitory effect of HU and SRJ23 in combination on the Jurkat cell line and determine the efficacy of the combination. Method: T-cell acute lymphoblastic leukaemia (Jurkat cells) was seeded and treated with different concentrations of SRJ23 and HU. After 96-hour incubation, an MTT assay was used to assess the in vitro growth inhibition of the combination drug (HU and SRJ23) against Jurkat cells. Then Compusyn software was used to determine the synergism of drug combinations obtained from MTT results. In addition, an apoptosis assay was conducted using FITC/propidium iodide (PI), and flow cytometry was done to confirm the apoptosis induced by the combination drug. Results: The dose-response curves indicated that combining 10 μM SRJ23 with either 125 μM HU (combination index 0.67) or 250 μM HU (combination index 0.57) resulted in a significant reduction in cell viability, reflecting a synergistic effect. These specific combinations were more effective at decreasing cell viability in proportion to the combined dose than other tested concentrations. This was determined by comparing the combination index and the effectiveness of cell viability reduction between the 10 μM SRJ23 with 125 μM HU or 250 μM HU combinations and other combinations of concentrations, and these synergistic combinations induced apoptosis. Conclusion: The combination of HU and SRJ23 demonstrated a synergistic effect against T-cell ALL Jurkat cells, leading to a notable inhibitory impact in vitro. Moreover, the combined treatment induced apoptosis, suggesting a promising new approach to targeted chemotherapy. The two agents together produced a significantly higher rate of apoptosis compared to when each was used individually.

Text FPSK(m) 2023 22 - Full Text.pdf Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (1MB) Text FPSK(m) 2023 22.pdf Restricted to Repository staff only Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (2MB)

Actions (login required)

View Item