title: Targeting hyaluronic acid production for the treatment of leukemia: treatment with 4-methylumbelliferone leads to induction of MAPK-mediated apoptosis in K562 leukemia.
abstract: The current study examined the effect of modulation of hyaluronic acid (HA) synthesis on leukemia cell survival using the hyaluronic acid synthesis inhibitor 4-methylumbelliferone (4-MU). Treatment of CML cells with 4-MU led to caspase-dependent apoptosis characterized by decreased HA production, PARP cleavage, and increased phosphorylation of p38. Addition of exogenous HA, the pan caspase inhibitor Z-VAD-FMK or the p38 inhibitor SB203580 to 4-MU treated cells was able to protect cells from apoptosis. Treatment of tumor-bearing mice with 4-MU led to a significant reduction in tumor load which was mediated through the induction of apoptosis.
authors.affiliation: Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, GA 31207, United States.
authors.forename: Olga N
authors.initials: ON
authors.lastname: Uchakina
authors.forename: Hao
authors.initials: H
authors.lastname: Ban
authors.forename: Robert J
authors.initials: RJ
authors.lastname: McKallip
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000096:biosynthesis*; D006923:Hymecromone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D020014:K562 Cells; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D006923:Hymecromone; D006820:Hyaluronic Acid; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Apoptosis; CML; Hyaluronic acid; p38