Tumor Suppressive functions of 4-MU on human AML cells modulation of senescence, CD44 expresion and mitochondria status.

PIBUEL M; ALVAREZ E.; LOMBARDO T; PAPADEMETRIO D,; LOMBARDIA S.; DIAZ M; POODTS D; HAJOS S

Mar del Plata

Congreso; Reunion Anual SAIC, SAI y SAFIS; 2018

SAIC- SAI- SAFIS

Beside the improvement in acute myeloid leukemia (AML) therapy, half of patients die due to complications related to treatment. CD44, the main hyaluronan receptor, has been proposed as a therapeutic target in AML. Down-regulation of this receptor has been associated to inhibition of proliferation and metabolic reprogramming including mitochondrial changes which sensitize to chemotherapy in different tumors. 4-methylumbelliferone (4MU) has shown promising effects as a potential new drug in cancer. Recently, it has been demonstrated that 4MU down-regulates CD44 expression in breast cancer cells. However, little is known about 4MU effects on hematological malignancies. Previous results in our lab showed that 4MU inhibited cell proliferation in a dose dependent manner in AML cell lines without inducing apoptosis at lower doses but showing Senescense Associated Heterochromatin Foci (SAHF+) cells by DAPI stain. Considering this, we hypothesize that 4MU would be a potential new drug for the treatment of acute leukemia. The aim of this work was to evaluate the effect of lower doses of 4MU on CD44 expression, senescence modulation and mitochondrial status in human AML cell line (U937). Results showed that treatment with 4MU reduces significantly total CD44 expression in a dose dependent manner as assessed by FC (p