High Expression of bcl-xL in K562 Cells and Its Role in the Low Sensitivity of K562 to Realgar-Induced Apoptosis

Abstract

Arsenic compounds (As₂O₃orAs₄S₄) have been used successfully for the treatment of acute promyelocytic leukemia (APL) for quite a long time. It has been noticed that the sensitivity to apoptosis induced by As₂O₃varies among various leukemia cells. It was reported by several groups that As₂O₃ could induce apoptosis in APL-derived NB4 cells at concentrations of 0.5–1 µmol/l, whereas in other leukemia cells like K562, As₂O₃ has no effects at the same concentration. K562 cells undergo apoptosis only when the concentration of As₂O₃is greater than 2 µmol/l. Another arsenic compound, realgar (As₄S₄), a traditional Chinese mineral medicine, has been used to treat APL effectively and demonstrated to have lower toxicity than As₂O₃. It would be interesting to know whether NB4 and K562 cells will show different sensitivity to realgar as well and if there is a difference, what is the cellular mechanism of it. In our present study, K562 cells were much less sensitive than NB4 cells to apoptosis induced by realgar. We confirm that the expression of bcl-x_L is significantly higher in K562 cells than that in NB4 cells and is not downregulated upon realgar treatment. K562 cells become sensitive to realgar at clinically acceptable concentrations when bcl-x_L expression level is downregulated by transfecting bcl-x_L antisense RNA vector into the cells. Our results suggest that the increased bcl-x_L expression in K562 cells contributes to its insensitivity to realgar-induced apoptosis.