Significance of intracellular arsenic trioxide for therapeutic response in acute promyelocytic leukemia

Arsenic trioxide (As2O3) is an effective drug for treatment of acute promyelocytic leukemia (APL) and malignant tumors. However, it is not commonly known to researchers that sensitivity has been associated with As2O3 concentration in target cells. Cell lines and cell strains of leukemia and solid cancer cells were treated with different concentrations of As2O3, and the concentrations were compared to apoptosis detected by FITC-annexin V and propidium iodide (PI) double staining. Results showed that intracellular and intercellular concentrations of arsenic in different cell lines differed. Our study noted that the cell lines had concentrations of arsenic trioxide in decreasing order, as follows: APL primary cell > K562 > CML primary cell > HL-60 > AML-M2 primary cell > HeLa > H-22. Higher intracellular As2O3 concentrations in cell lines APL, NB4, and K562 can be obtained by treating in culture medium with lower As2O3 concentration for longer times than the transient higher concentration. These results indicate that different leukemia and solid carcinoma cell lines have different intracellular arsenic concentrations, which correlate with different sensitivities to As2O3 in clinical treatment. The intracellular As2O3 concentration is higher; in addition, we note apoptosis, a very important observation in our study. As2O3 inhibited the growth of these cell lines significantly. Novel techniques by maintaining continuous low but effective arsenic levels inside the target leukemic cells in APL may improve the complete remission rate and overall survival with minimum cost and drug toxicity. (C) 2005 Wiley-Liss, Inc.