Relation between ABCB1 overexpression and COX2 and ALOX5 genes in human erythroleukemia cell lines

• Published in: Prostaglandins & other lipid mediators Vol. 155; p. 106553
• Main Authors: Salgado, Mariana Teixeira Santos Figueiredo, Lopes, Alessandra Costa, Fernandes e Silva, Estela, Cardoso, Julia Quarti, Vidal, Raphael Silveira, Cavalcante-Silva, Luiz Henrique Agra, Carvalho, Deyse Cristina Madruga, Machado, Karina dos Santos, Rodrigues-Mascarenhas, Sandra, Rumjanek, Vivian Mary, Votto, Ana Paula de Souza
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2021
• Subjects: Arachidonate 5-Lipoxygenase - genetics; Arachidonate 5-Lipoxygenase - metabolism; ATP Binding Cassette Transporter, Subfamily B - genetics; ATP Binding Cassette Transporter, Subfamily B - metabolism; Cell Line, Tumor; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Cyclooxygenases; Drug Resistance, Neoplasm - drug effects; Drug Resistance, Neoplasm - genetics; Humans; Hydroxyurea - analogs & derivatives; Hydroxyurea - pharmacology; Inflammation; K562 Cells; Leukemia, Erythroblastic, Acute - genetics; Leukemia, Erythroblastic, Acute - metabolism; Leukemia, Erythroblastic, Acute - pathology; Lipoxygenases; MDR phenotype; P-glycoprotein; P-glycoprotein; Lipoxygenases; Cyclooxygenases; Inflammation; MDR phenotype
• ISSN: 1098-8823
• DOI: 10.1016/j.prostaglandins.2021.106553

•K562-Lucena and FEPS show a direct relationship between the COX2 and ABCB1 genes.•The ABCB1 and COX2 genes are inversely related to ALOX5.•ABCB1 can play a regulatory role in COX2 and ALOX5 in leukemia cells line.•Increased expression of COX2 and decreased ALOX5 is related to overexpression ABCB1. This study aimed to characterize the relationship between the COX2 and ALOX5 genes, as well as their link with the multidrug resistance (MDR) phenotype in sensitive (K562) and MDR (K562-Lucena and FEPS) erythroleukemia cells. For this, the inhibitors of 5-LOX (zileuton) and COX-2 (acetylsalicylic acid-ASA) and cells with the silenced ABCB1 gene were used. The treatment with ASA caused an increase in the gene expression of COX2 and ABCB1 in both MDR cell lines, and a decrease in the expression of ALOX5 in the FEPS cells. Silencing the ABCB1 gene induced a decrease in COX2 expression and an increase in the ALOX5 gene. Treatment with zileuton did not alter the expression of COX2 and ABCB1. Cytometry data showed that there was an increase in ABCB1 protein expression after exposure to ASA. In addition, the increased activity of ABCB1 in the K562-Lucena cell line indicates that ASA may be a substrate for this efflux pump, corroborating the molecular docking that showed that ASA can bind to ABCB1. Regardless of the genetic alteration in COX2 and ABCB1, the direct relationship between these genes and the inverse relationship with ALOX5 remained in the MDR cell lines. We assume that ABCB1 can play a regulatory role in COX2 and ALOX5 during the transformation of the parental cell line K562, explaining the increased gene expression of COX2 and decreased ALOX5 in the MDR cell lines.