Arsenic trioxide (ATO) is known to have concentration-dependent dual effects on acute promyelocytic leukemia (APL) cells, preferentially inducing apoptosis at relatively high concentrations and promoting partial differentiation at low concentrations. Protein phosphatase 2A (PP2A) has been demonstrated to take part in the differentiation and apoptosis of malignant hematological cells induced by commonly used medicines, such as all-transretinoic acid (ATRA), interferon, arsenic sulfide, etc. However, there are almost no data on the role PP2A plays in ATO-induced APL cell differentiation/apoptosis. In this report, our goal was to show that ATO inhibited the proliferation and induced the apoptosis and differentiation of neuroblastoma NB4 cells. Okadaic acid (OKA), a specific inhibitor of protein phosphatase activity, markedly increased these effects of ATO on cells. To further elucidate the regulation of PP2A during ATO-induced differentiation/apoptosis of NB4 cells, we measured the phosphatase activity and protein expression of PP2A. The activity of PP2A in NB4 cells decreased with increasing concentration of ATO. This decrease of PP2A activity appeared to parallel phenotypic and functional changes of NB4 cells. Western blot analysis showed that the levels of the PP2A structural subunit PP2A-A decreased during the course of ATO-induced differentiation/apoptosis, whereas the expression of the B and C subunits of PP2A was relatively unaltered. In conclusion, the decrease of PP2A activity may be involved in ATO-induced apoptosis and differentiation of APL cells, and this decrease is predicted to be related to the repression of PP2A-A subunit expression.

Download full-text PDF

Source
http://dx.doi.org/10.1358/mf.2008.30.6.1186086DOI Listing

Publication Analysis

Top Keywords

nb4 cells
20
protein phosphatase
12
pp2a activity
12
cells
9
pp2a
9
differentiation apoptosis
8
apl cells
8
apoptosis differentiation
8
phosphatase activity
8
ato-induced differentiation/apoptosis
8

Similar Publications

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 PDF

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 PDF

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 PDF

Immunomodulation in biotechnological processes requires an adequate level of specific, high-affinity recombinant antibodies expressed in the affected cells. Here, we report a new strategy to obtain a sensitive nanobody against the 2,4-dichlorophenoxyacetic acid (2,4-D) herbicide. Unlike the previous methods that used total peripheral blood lymphocytes, specific peripheral lymphocytes stained with a fluorescein isothiocyanate-labeled 2,4-D coating antigen were isolated via fluorescence-activated cell sorting and used for phage display library construction.

View Article and Find Full Text PDF

Efficient gene transduction and cell viability are critical factors in genetic manipulation for research and therapeutic purposes. In this study, we explored the challenges associated with transducing the NB-4 cell line, a well-established model for acute promyelocytic leukemia (APL), using lentiviral vectors. While the initial transduction efficiency in NB-4 cells reached approximately 30%, we observed a significant decrease in cell viability, a phenomenon not observed in other acute leukemia cell lines such as THP-1 cells.

View Article and Find Full Text PDF

Want 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!