The adhesion molecule CD44 variant isoform (CD44v6) closely associates with progress of acute myeloid leukemia (AML). This study was purposed to investigate the effects of all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3) on the expression of CD44v6 and the associated signal pathway phosphatidylinositol 3-kinase (PI3K)/Akt in acute promyelocytic leukemia (APL) cell line NB4 cells. The differentiation of NB4 was detected by morphologic observation and flow cytometry; the NB4 cell apoptosis was assayed by flow cytometry with Annexin V-FITC/PI double staining; the CD44v6 mRNA expression in NB4 cells was determined by real-time RT-PCR, the CD44v6 protein expression and changes of PI3K/Akt signal pathway in NB4 cells were analysed by Western blot. The results demonstrated that in ATRA-induced differentiation, the transcriptional level of CD44v6 was dominantly down-regulated, the translational level of CD44v6 did not change and the PI3K/Akt signal axis was activated. In As2O3-induced apoptosis, both the transcriptional level and translational level of CD44v6 were remarkably reduced, and the PI3K/Akt pathway was inhibited. It is concluded that the regulation of ATRA on expression of CD44v6 in NB4 cells differs from that of As2O3. The results provide an experimental basis to reveal the different mechanism of ATRA and As2O3 in view of the intercommunication between leukemia cells and hematopoietic microenvironment.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
A novel therapeutic strategy for leukopenia: Miltefosine activates the Ras/MEK/ERK pathway to promote neutrophil differentiation.
Biochem Biophys Res Commun
February 2025
Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, China. Electronic address:
Leukopenia, marked by diminished white blood cell (WBC) counts, presents significant challenges in the management of hematological malignancies and immunocompromised patients. This study evaluated the therapeutic potential of miltefosine (MFS), a phospholipid analogue, for treating leukopenia. In vitro studies using HL60 and NB4 cells revealed that MFS effectively promoted neutrophil differentiation and function, evidenced by the upregulation of surface markers CD11b, CD11c, CD14, and CD15, as well as enhanced bactericidal activity assessed through the NBT reduction assay.
View Article and Find Full Text PDFCombination of triciribine and p38 MAPK inhibitor PD169316 enhances the differentiation effect on myeloid leukemia cells.
PLoS One
December 2024
Department of Clinical Laboratory, Tohoku Medical and Pharmaceutical University Hospital, Sendai, Japan.
Differentiation therapy with all-trans retinoic acid (ATRA) is well established for acute promyelocytic leukemia (APL). However, the narrow application and tolerance development of ATRA remain to be improved. A number of kinase inhibitors have been reported to induce cell differentiation.
View Article and Find Full Text PDFRapamycin and Niacin combination induces apoptosis and cell cycle arrest through autophagy activation on acute myeloid leukemia cells.
Mol Biol Rep
December 2024
Faculty of Life and Natural Sciences, Department of Bioengineering, Abdullah Gül University, Sumer Campus, Kayseri, 38080, Turkey.
Background: Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy caused by disorders in stem cell differentiation and excessive proliferation resulting in clonal expansion of dysfunctional cells called myeloid blasts. The combination of chemotherapeutic agents with natural product-based molecules is promising in the treatment of AML. In this study, we aim to investigate the anti-cancer effect of Rapamycin and Niacin combination on THP-1 and NB4 AML cell lines.
View Article and Find Full Text PDFUnveiling the link between NADPH oxidase 2 activation and mitochondrial superoxide formation in leukemic cell killing induced by arsenic trioxide.
Pharmacol Res
January 2025
Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy. Electronic address:
This study focused on the interplay between NADPH oxidase 2 (NOX 2) activation and mitochondrial superoxide (mitoO) formation induced by clinically relevant concentrations of arsenic trioxide (ATO; AsO) in acute promyelocytic leukemia (APL) cells. Carefully controlled inhibitor studies and small interfering RNA mediated downregulation of p47 (a component of the NOX 2 complex) expression demonstrated that, in an APL cell line, ATO promotes upstream NOX 2 activation critically connected with the formation of mitoO and with the ensuing mitochondrial permeability transition (MPT)-dependent apoptosis. Instead, acute myeloid leukemia (AML) cell lines respond to ATO with low NOX 2 activation, resulting in a state that is non-permissive for mitoO formation.
View Article and Find Full Text PDFImidazolium, pyridinium and pyrazinium based ionic liquids with octyl side chains as potential antibacterial agents against multidrug resistant uropathogenic .
Heliyon
November 2024
Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, 44000, Pakistan.
Urinary tract infections (UTIs) are the second most prevalent infectious disease with being the most common etiological agent behind these infections, affecting more than 150 million people globally each year. In recent decades, the emergence of multi-drug resistant (MDR) pathogens has rapidly escalated. To combat antimicrobial resistance (AMR), it is important to synthesize new biologically effective alternatives like ionic liquids (ILs) to control the bacterial infection and their spread.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!