Abstract
Chronic myeloid leukemia (CML), a myeloproliferative disorder characterized by the BCR-ABL oncoprotein, presents its treatment based on tyrosine kinase inhibitors (TKIs), mainly imatinib. However, despite its clinical success, almost 30% of all CML patients demand alternative therapy. In this context, the development of drugs capable of overcoming TKIs resistance is imperative. The pterocarpanquinone-LQB-118 is a novel compound with anti-tumor effect in CML cells whose mechanism of action is being elucidated. Here, we demonstrate that in two CML cell lines exhibiting different biological characteristics, LQB-118 modulates NFκB subcellular localization, apparently independently of the AKT and MAPK pathways, partially inhibits proteasome activity, and alters the expression of microRNAs -9 and -21.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antineoplastic Agents / chemical synthesis
-
Antineoplastic Agents / chemistry
-
Antineoplastic Agents / pharmacology*
-
Cell Proliferation / drug effects
-
Dose-Response Relationship, Drug
-
Drug Screening Assays, Antitumor
-
Humans
-
K562 Cells
-
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
-
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
-
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
-
MicroRNAs / genetics
-
MicroRNAs / metabolism*
-
Molecular Structure
-
NF-kappa B / metabolism*
-
Naphthoquinones / chemical synthesis
-
Naphthoquinones / chemistry
-
Naphthoquinones / pharmacology*
-
Proteasome Endopeptidase Complex / metabolism
-
Protein Kinase Inhibitors / chemical synthesis
-
Protein Kinase Inhibitors / chemistry
-
Protein Kinase Inhibitors / pharmacology*
-
Pterocarpans / chemical synthesis
-
Pterocarpans / chemistry
-
Pterocarpans / pharmacology*
-
Structure-Activity Relationship
Substances
-
Antineoplastic Agents
-
LQB 118
-
MIRN21 microRNA, human
-
MIRN92 microRNA, human
-
MicroRNAs
-
NF-kappa B
-
Naphthoquinones
-
Protein Kinase Inhibitors
-
Pterocarpans
-
Proteasome Endopeptidase Complex