Effects of arsenic trioxide, all-trans-retinoic acid and dexamethasone on NB4 cell line

ABSTRACT

Experimental and preclinical observations have indicated that combination therapy with all-trans-retinoic acid [ATRA] and arsenic trioxide [ATO] may strongly enhance their therapeutic effects in the treatment of acute promyelocytic leukemia [APL]. Whilst dexamethasone [Dex] is routinely used for the control of APL-differentiation syndrome, its effect on the pharmacodynamics of ATO is not clear. Therefore, in this study, effects of therapeutic concentrations of ATO, ATRA and Dex and their sequential usages on the proliferation, differentiation and apoptosis in t [15;17]-positive NB4 cells was investigated. Cells were treated with therapeutic concentrations of ATO, ATRA and Dex either as single or in combination and cell proliferation was assessed by XTT assay. Expression of CD lib as an indicator of cell differentiation and the percentage of 7-AAD positive cells as a marker of apoptosis were determined by flow cytometry. ATO, but not ATRA and Dex, decreased proliferation of the cells dose-dependently. Pre-treatment of the cells with any of the drugs did not alter the effects of other drugs on the proliferation. Pre-treatments with Dex blocked the apoptotic effect of ATO [1 micro M]. No improvement or antagonistic effects was observed with the pretreatment/ combination of the ATO and ATRA on the differentiation and apoptosis of the cells. It is possible that concomitant usage of Dex with apoptotic doses of ATO in APL patients counteract therapeutic effects of ATO