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: Olga N Uchakina, Hao Ban, Robert J McKallip
• Journal: Leukemia research (Leuk Res) Vol. 37 Issue 10 Pg. 1294-301 (Oct 2013) ISSN: 1873-5835 [Electronic] England
• PMID: 23876826 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Hymecromone
• Hyaluronic Acid
• Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Antineoplastic Agents (administration & dosage, pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Disease Models, Animal
• Extracellular Space (metabolism)
• Humans
• Hyaluronic Acid (biosynthesis)
• Hymecromone (administration & dosage, analogs & derivatives, pharmacology)
• K562 Cells
• Leukemia (metabolism, pathology)
• Mice
• Mitogen-Activated Protein Kinases (metabolism)
• Tumor Burden (drug effects)
• Xenograft Model Antitumor Assays
• p38 Mitogen-Activated Protein Kinases (metabolism)