Title
Molecular determinants of etoposide resistance in HL60 cells
Authors
Rasha H. Alghamdi#,1, 2, 3,Farid Ahmed#,*,1,4, Sara M. Ibrahim2, Peter N. Pushparaj1,4, Hans Jurgen Schulten1, Adel M. Abuzenadah1,4,5 & Abdulrahman L. Almalki2
Affiliation
1Center of Excellence in Genomic Medicine Research, King Abdulaziz University, P.O. Box 80216, Jeddah21589, Kingdom of Saudi Arabia; 2Department of Biochemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80218, Jeddah21589, Kingdom of Saudi Arabia; 3Department of Chemistry, Faculty of Science, Taif University, P. O. Box 11099, Taif 21944, Kingdom of Saudi Arabia; 4Faculty of Applied Medical Sciences, King Abdulaziz University, P.O. Box 80216, Jeddah, 21589, Kingdom of Saudi Arabia; 5King Fahad Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah21589, Kingdom of Saudi Arabia; #Both authors contributed equally, *Corresponding author; #Equal contribution
Farid Ahmed- E-mail: fahmed1@kau.edu.sa
Rasha H Alghamdi -E-mail: ralghamdi01@gmail.com
Sara M Ibrahim – Email: saramohd88@gmail.com
Peter N Pushparaj – Email: peter.n.pushparaj@gmail.com
Hans Jurgen Schulten- Email: hschult2@msn.com
Adel M Abuzenadah – Email: aabuzenadah@kau.edu.sa
Abdulrahman L Almalki – Email: alalmalki@kau.edu.sa
Article Type
Research Article
Date
Received September 2, 2022; Revised October 3, 2022; Accepted October 17, 2022, Published October 31, 2022
Abstract
Chemotherapy resistance is the main reason for treatment failure in acute myeloid leukemia (AML) and the major cause of its mortality. Etoposide is a DNA topoisomerase-II inhibitor that is used either as a single agent or in combination with cytarabine, azacytidine, vinca alkaloids, and anthracyclines for the treatment of relapsed /refractory AML. In this study, we sought to determine and understand the mechanism of etoposide resistance in AML using the HL60 cell line.HL60 cells were treated with incremental doses of etoposide and resistant colonies were isolated by culturing the resistant cells in semi-solid culture media. Three clones were selected for etoposide resistance namely, HL60-EtopR H1A, HL60-EtopR H1B, and HL60-EtopR H1C which demonstrated 4.78, 2.39, and 4.42-fold higher resistance to etoposide compared with the parental cells. To determine molecular differences between the etoposide-resistant HL60-EtopR cells and the parental cells, microarray-based gene expression profiling was performed. We found up regulation of members of the src tyrosine kinase family genes in the etoposide resistant cells. Further studies are required to evaluate the role of Src inhibitors in targeting etoposide resistant cells.
Keywords
Cancer, Chemotherapy, Multidrug Resistance, Etoposide, Apoptosis, Acute Myeloid Leukemia
Citation
Alghamdi et al. Bioinformation 18(10): 894-899 (2022)
Edited by
P Kangueane
ISSN
0973-2063
Publisher
License
This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.
