title: NFκB pathway and microRNA-9 and -21 are involved in sensitivity to the pterocarpanquinone LQB-118 in different CML cell lines.
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.
authors.forename: Fernanda Costas C
authors.initials: FC
authors.lastname: de Faria
authors.forename: Maria Eduarda Bento
authors.initials: ME
authors.lastname: Leal
authors.forename: Paula Sabbo
authors.initials: PS
authors.lastname: Bernardo
authors.forename: Paulo R R
authors.initials: PR
authors.lastname: Costa
authors.forename: Raquel C
authors.initials: RC
authors.lastname: Maia
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism*; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D036343:Pterocarpans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; C569361:LQB 118; C524940:MIRN21 microRNA, human; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D009285:Naphthoquinones; D047428:Protein Kinase Inhibitors; D036343:Pterocarpans; D046988:Proteasome Endopeptidase Complex