Interaction between Gallic acid and Asparaginase to potentiate anti-proliferative effect on lymphoblastic leukemia cell line

Background: Treatment of acute lymphoblastic leukemia (ALL) fails in some cases and the side effects cause mortality in certain patients. Gallic acid (GA), a polyhydroxyphenolic compound has biological functions including anti-proliferative properties. The aim of the present study was to investigate the growth inhibition effects of GA in combination with asparaginase (ASP), as a component of combination chemotherapy, in a lymphoblastic leukemia cell line. Methods: Jurkat cells were incubated with different concentrations of GA with or without ASP. Proliferation inhibition was investigated using MTS test. The level of apoptosis alterations were evaluated using flow cytometry. The expression of Fas gene level and surface expression were investigated by quantitative real time PCR and flow cytometry respectively. Results: GA at 50 mu M concentration and ASP at 0.5 IU/ml inhibited 50% cell proliferation in 48 hours. GA also increased the inhibitory effect of ASP and some combinations had synergistic results. The increase of cell apoptosis and Fas expression were observed in GA-treated cells compared to control. GA increased the effect of ASP on proliferation inhibition, induction of apoptosis and Fas expression. Conclusion: GA is an effective component in proliferation inhibition, apoptosis induction and enhancement of Fas expression level in Jurkat cell line. GA in some combination with ASP increases the effect of the latter on the cells. The study of the mechanism of these effects could be a further step towards target therapy. This study is a preliminary phase to the use of GA and should be carried out by more comprehensive study and animal models.