The effect of isosorbide on gelatinase-A and gelatinase-B activity in leukemic cell lines

Gelatinases are a subgroup of matrix metalloproteinases (MMPs) and have an important role in tumor growth and angiogenesis. In this regard, MMP-2 (gelatinase A) and MMP-9 (gelatinase B) have particular value. Isosorbide dinitrate (a nitric oxide donor) has been broadly used in treatment of cardiac diseases and its inhibitory effect on angiogenesis and tumor growth have been reported in vivo. In this study, the effect of isosorbide dinitrate on gelatinase-A and gelatinase B activity in leukemic cell lines has been assessed in vitro. MOLT-4, JURKAT and U937 leukemic cells were cultured in complete RPMI medium and then incubated with different concentrations of isosorbide (4 × 10-7, 4 × 10-6, 4 × 10-5, 4 × 10-4 M) in the presence of phorbol myristate acetate (PMA) (25 ng/mL), as a gelatinase inducer, for 24 hours. Afterwards, the gelatinase A and B activity in the cell culture medium was evaluated by gelatin zymography. The gelatinase A and B activity of MOLT-4, JURKAT and U937 leukemic cells treated with isosorbide did not show any significant difference with control. The gelatinase A activity was 1 ± 0.0 and 1.04 ± 0.06 in the control and 4 × 10-4 M concentration of the isosorbide in MOLT-4 cell line, respectively. In this study, isosorbide did not show any significant effect on gelatinase A and B activity in leukemic cells. The anti-tumoral and anti- angiogenic effect of isosorbide was reported by others to be possibly due to non-gelatinase activity mediated mechanism.