[Growth inhibitory and apoptotic effects of carbenoxolone in human leukemia K562 cell line]

ABSTRACT

Leukemia is a malignant and progressive disorder in which genetic defects in hematopoietic cells lead to uncontrolled proliferation of blood cells. Different drugs have been proposed for the treatment of leukemia but none of them resulted in complete remission. Recently, anti-cancer effects of carbenoxolone [CBX], that is a 3- hemisuccinate, have been reported in several cell lines. In the present study we evaluated the effects of CBX on K562 cell line as an experimental model of chronic myeloid leukemia [CML]. K562 cells were cultured and treated for various time intervals with different concentrations of CBX [50-300 micro M]. Trypan blue exclusion test and tetrazolium salt absorption test [MTT] were used to evaluate the growth inhibitory and apoptotic effects of the drug. Fluorescence microscopy and DNA fragmentation assay were used to study apoptosis. The results of this study showed that CBX induced growth inhibition of K562 cells in a dose- and time- dependent manner. For example, growth inhibition rates after 48 hours treatment with concentrations of 50 micro m, 100 micro m, 150 micro m, 200 micro m and 300 micro m were 11%, 41%, 59%, 79% and 92%, respectively. Furthermore results of fluorescence microscopy and DNA fragmentation assays indicated that apoptosis, is the cause of cell death induced by CBX. Considering the growth inhibitory and apoptotic effects of CBX on human myeloid leukemia K562 cells, the drug can be considered as a potential candidate for further studies on CML treatment