A two-pronged anti-leukemic agent based on a hyaluronic acid-green tea catechin conjugate for inducing targeted cell death and terminal differentiation.

Abstract	Acute myeloid leukemia (AML) is an aggressive malignancy that leads to a poor prognosis even with intensive chemotherapy. As the key feature of AML is the blockade of hematopoietic cell maturation, considerable attention has been paid to 'differentiation therapy' aimed at transforming AML cells into more mature, benign phenotypes using pharmacological agents. Here we report a hyaluronic acid-(-)-epigallocatechin-3-O-gallate (HA-EGCG) conjugate as a unique anti-leukemic agent, capable of selectively killing AML cells as well as promoting their terminal differentiation into monocytes and granulocytes. This 'two-pronged' effect of the HA-EGCG conjugate was demonstrated in two different AML cell lines (NB4 and HL60), but absent in a physical mixture (HA + EGCG), highlighting the importance of HA conjugation for targeting of EGCG moieties to AML cells. Moreover, administration of the HA-EGCG conjugate not only suppressed AML progression, but also prolonged survival in the HL60 xenograft mouse model. Our study suggests new opportunities for designing two-pronged anti-leukemic agents for more effective AML treatment.
Authors	Kun Liang , Ki Hyun Bae , Akiko Nambu , Bibek Dutta , Joo Eun Chung , Motomi Osato , Motoichi Kurisawa
Journal	Biomaterials science (Biomater Sci) Vol. 8 Issue 1 Pg. 497-505 (Dec 17 2019) ISSN: 2047-4849 [Electronic] England
PMID	31761907 (Publication Type: Journal Article)
Chemical References	Catechin Hyaluronic Acid epigallocatechin gallate
Topics	Animals Antineoplastic Combined Chemotherapy Protocols (administration & dosage, chemistry, pharmacology) Catechin (administration & dosage, analogs & derivatives, chemistry, pharmacology) Cell Death (drug effects) Cell Differentiation (drug effects) Cell Line, Tumor Cell Proliferation (drug effects) HEK293 Cells HL-60 Cells Human Umbilical Vein Endothelial Cells Humans Hyaluronic Acid (administration & dosage, chemistry, pharmacology) Leukemia, Myeloid, Acute (drug therapy) Male Mice Xenograft Model Antitumor Assays

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