Targeting hyaluronic acid production for the treatment of leukemia: Treatment with 4-methylumbelliferone leads to induction of MAPK-mediated apoptosis in K562 leukemia

Inhibition of hyaluronan synthesis restores immune tolerance during autoimmune insulitis

“…4-MU has been mostly used in animal models to prevent tumor metastasis, in which HA is thought to drive angiogenesis and tumor proliferation (38)(39)(40). A handful of reports suggest that 4-MU may also have utility in other inflammatory settings (9,41).…”

Spiroquinazolinone-induced cytotoxicity and apoptosis in K562 human leukemia cells: alteration in expression levels of Bcl-2 and Bax

“…Briefly, after double washing of treated and untreated cells with PBS, 1 × 10 6 cells were resuspended in binding buffer (10 mM HEPES/NaOH, pH 7.4, 140 mM NaCl, 2.5 mM CaCl 2 ) and then 10 μL of Annexin-V FITC and 10 μL PI were added. The mixture was incubated for 15 min in the dark at room temperature and then measured by flow cytometry (Partec PAS) (Uchakina et al, 2013).…”

Hyaluronan stimulates pancreatic cancer cell motility

“…Because we found that treatment with 4-MU robustly attenuates the migratory ability of PDAC cells, inhibiting HA production could be an ideal therapeutic strategy to prevent invasion and/or metastasis of PDAC. In fact, inhibition of HA synthesis by treatment with 4-MU, or its derivative 4-methylesculetin, has demonstrated antitumor activity in a variety of cancers, including PDAC [32][33][34][35][36][37]. Of particular importance, 4-MU (or hymecromone) is a dietary supplement for improving liver health and can be administered orally without any toxicities [38].…”