The hyaluronan synthesis inhibitor 4-methylumbelliferone inhibits cell proliferation and wound healing on in vitro endometriosis models

CARLA OLIVARES; FLORENCIA CHIAPPINI; BÁRBARA MC CORMACK; DANIELA MADANES; ANDREA RANDI; ROSA BARAÑAO; GABRIELA MERESMAN

Buenos Aires

Congreso; 8th Latin American Symposium on Maternal-Fetal Interaction and Placenta; 2019

International Federation of Placenta Associations 2019 (IFPA2019)

Objectives: The aim of this study was to evaluate the effect of 4-methyl-umbelliferone (4MU) on cell proliferation, wound healing process andgelatinase activity on human endometrial stromal (t-HESC) or epithelial(ECC-1) cell lines.Methods: t-HESC and ECC-1 endometrial cell lines were stimulated withdifferent concentrations of 4MU. Cell proliferation was evaluated after24hs with the cell proliferation reagent WST-1. The area of a scratch closedby the t-HESC was calculated in a wound healing assay, for this purposephotomicrographs were taken at time 0h and time 20hs; and the gelati-nase activity in conditioned media of t-HESC was evaluated by zimog-raphy. Only p<0.05 was considered as statistically significant.Results: After 24hs of treatment the cell proliferation of ECC-1 wassignificantly inhibited by 0.5, 1 and 2 mM 4MU (p<0.01, p<0.001 andp<0.01, respectively versus control), whereas cell proliferation of t-HESC was significantly inhibited by 2 and 4 mM 4MU (p<0.01 versuscontrol). Already at 0.5 mM 4MU, the migration of t-HESC cells wassignificantly inhibited and the scratch was closed in a low percentage(p<0.01 for 0.5 and 1 mM 4MU versus control, p<0.001 for 2 and 4 mM4MU). Preliminary results of MMP-2 and MMP-9 activities revealed thatthese gelatinases would not be modulated after 24hs of 4MUtreatment.Conclusion: Endometriosis is a benign gynecological disease affecting 10%of women of reproductive age, characterized by the presence of endo-metriotic foci outside the uterine cavity. Previous studies from our labo-ratory demonstrated a strong antiangiogenic activity of 4MU. The presentresults are, in part, in agreement with those reported by other authors.