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.
Keywords: Cancer, chronic myeloid leukemia, microRNA, multidrug resistance phenotype, NFκB, pterocarpanquinone-LQB-118.
Graphical Abstract
Anti-Cancer Agents in Medicinal Chemistry
Title:NFκB Pathway and microRNA-9 and -21 are Involved in Sensitivity to the Pterocarpanquinone LQB-118 in Different CML Cell Lines
Volume: 15 Issue: 3
Author(s): Fernanda Costas C. de Faria, Maria Eduarda Bento Leal, Paula Sabbo Bernardo, Paulo R.R. Costa and Raquel C. Maia
Affiliation:
Keywords: Cancer, chronic myeloid leukemia, microRNA, multidrug resistance phenotype, NFκB, pterocarpanquinone-LQB-118.
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.
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Cite this article as:
de Faria Costas C. Fernanda, Bento Leal Eduarda Maria, Bernardo Sabbo Paula, Costa R.R. Paulo and Maia C. Raquel, NFκB Pathway and microRNA-9 and -21 are Involved in Sensitivity to the Pterocarpanquinone LQB-118 in Different CML Cell Lines, Anti-Cancer Agents in Medicinal Chemistry 2015; 15 (3) . https://dx.doi.org/10.2174/18715206113139990108
DOI https://dx.doi.org/10.2174/18715206113139990108 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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