Effects of hyaluronan and its synthesis inhibitor 4-methylumbelliferone on human classic Hodgkin Lymphoma cell lines.

PIBUEL MATÍAS; PAPADEMETRIO DANIELA L; PAGLILLA NADIA A.; POODS DANIELA; RANUNCOLO STELLA MARIS; DÍAZ, MARIÁNGELES; HAJOS SILVIA E; LOMPARDIA SILVINA L

Cardiff

Congreso; 12th International Conference of the International Society for Hyaluronan Sciences.; 2019

International Society for Hyaluronan Sciences.

Hodgkin lymphoma (HL) is one of the most frequent lymphomas derived from the germinal centre.Even though its early diagnosis achieves high levels of complete remission, many patients relapse, become refractory to treatment or die due to conventional therapy related complications. One of the current challenges consist in the discovery of alternatives therapies. In line with this, tumour microenvironment has become a relevant target to be studied. Hyaluronan, is the main glycosaminoglycan (GAG) of the extracellular matrix and it has been shown that an increase of this GAG on patient biopsies correlates with a poor outcome. 4-methylumbelliferone (4MU), the hyaluronan (HA) inhibitor, is a curmarin derivative approved for its use as a choleretic agent in Europe and Asia, which has shown no toxicity. Although it has been proposed as a potential anti-tumour compound, there are no reports of its effects in human HL models. In connection with our previous results that show an important antiproliferative effect of 4MU in leukemia cell lines and its capability to sensitize these cells to different chemotherapeutic agents, we hypothesize that this drug could act similarly for LH. The aim of this work was to evaluate the effects of 4MU in classic HL human (cHL) cell lines, to assess if its effects are prevented by the addition of HA and if this drug is efficient to sensitize cells to vincristine (VCR) and doxorrubicine (DOX) effect. For that purpose, KM-H2, U-HO1, L-1236 and HDLM-2 cell lines were treated with 4MU (0,1, 0,5, 0,75 and 1 mM), high molecular weight HA, VCR, DOX and combinatorial conditions for 72 h. Results show that 4MU decreases the metabolic activity of all the evaluated cell lines in a dose-dependent manner (p