4-methylumbelliferone down-regulates CD44 expression, modulates mitochondrial status and sensitizes acute leukemia cells to the effects of vincristine.

Cardiff

Congreso; Hyaluronan Meeting 2019; 2019

ISHAS

Despite the improvement in acute myeloid leukemia (AML) therapy, half of patients die due to complications related to treatment. 4-methylumbelliferone (4MU), the inhibitor of hyaluronan synthesis, has shown promising effects as a potential new drug in cancer, but little is know about its effects on oncohematological malignancies. Recently, it has been demonstrated that this cumarin derivative modulates other players of hyaluronan metabolism, like its receptor CD44. This transmembrane glycoprotein has been proposed as a therapeutic target in AML and its down-regulation has been associated to inhibition of cell proliferation, modulation of matrix-remodeling enzimes and metabolic reprogramming which sensitize different tumors to chemotherapy. Previous results of our lab showed that 4MU inhibited cell proliferation in a dose dependent manner in leukemia cell lines and it was successful to sensitize K562 cell lines to vincristine (VCR) and imatinib effects. Considering this, we hypothesize that 4MU would be a potential new drug for the treatment of leukemia. The aim of this work was to evaluate the effect of 4MU on CD44 expression, metalloproteinase (MMP) activity and mitochondrial status on leukemia cell lines analizing if it was capable of sensitizing these cells to the effect of VCR. Results showed that treatment with 4MU reduced CD44 expression significantly in a dose dependent manner as assessed by FC (p