Abstract
The aim of the present study was to investigate the effects of the novel polyamine analog tetrabutyl propanediamine (TBP) on the growth of K562 chronic myelogenous leukemia (CML) cells and the underlying mechanism of these effects. MTT was used for the analysis of cell proliferation and flow cytometry was performed to analyze cell cycle distribution. DNA fragmentation analysis and Annexin V/propidium iodide double staining were used to identify apoptotic cells. The activity of the key enzymes in polyamine catabolism was detected using chemiluminescence. TBP can induce apoptosis and significantly inhibit K562 cell proliferation in a time- and dose-dependent manner. TBP treatment significantly induced the enzyme activity of spermine oxidase and acetylpolyamine oxidase in K562 cells, and also enhanced the inhibitory effect of the antitumor drug doxorubicin on K562 cell proliferation. As a novel polyamine analog, TBP significantly inhibited proliferation and induced apoptosis in K562 cells by upregulating the activity of the key enzymes in the polyamine catabolic pathways. TBP also increased the sensitivity of the K562 cells to the antitumor drug doxorubicin. These data indicate an important potential value of TBP for clinical therapy of human CML.
Highlights
Chronic myelogenous leukemia (CML), one of the three most common forms of leukemia, is a hematopoietic stem cell disease which is mostly caused by abnormal expression of the oncoprotein BCR‐ABL [1,2]
tetrabutyl propanediamine (TBP) has been demonstrated to inhibit the growth of solid tumor cell lines, including HepG2 and MG63 cells [11,12]
The present data revealed that TBP treatment significantly inhibited K562 cell proliferation and induced G0/G1‐phase arrest in a time‐ and dose‐dependent manner
Summary
Chronic myelogenous leukemia (CML), one of the three most common forms of leukemia, is a hematopoietic stem cell disease which is mostly caused by abnormal expression of the oncoprotein BCR‐ABL [1,2]. Hematopoietic stem cell transplantation is regarded as the most effective treatment for CML, but it is limited by numerous factors, including the availability of a donor, transplant rejection and the high expense [5]. For these reasons, it is necessary to develop novel methods for CML therapy. Growth inhibition and apoptosis can be induced in tumor cells by reducing the polyamine concentration [8]. TBP has been demonstrated to inhibit the growth and migration of human hepatocellular carcinoma HepG2 and osteosarcoma MG‐63 cells by inducing apoptosis [11,12].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
