Arsenic Trioxide Induces Apoptosis In Chronic Lymphocytic Leukemic Cells Through Down-Regulation Of Survivin Via The p53-Dependent Signaling Pathway

Arsenic trioxide induces cell apoptosis in a variety of tumor cells. However, the molecular mechanism underlying the killing effects of arsenic trioxide on tumor cells is not fully understood. Here, we demonstrate a signal pathway of arsenic trioxide treatment that leads to apoptosis in a B-cell chronic lymphocytic leukemia (WSU-CLL) cell line. Arsenic trioxide treatment significantly inhibited proliferation and induced apoptosis of WSU-CLL cells in a time- and dose-dependent manner. This anti-tumor effect of arsenic trioxide on WSU-CLL cells was mediated through the down-regulation of survivin and up-regulation of p53. Knock-down of intracellular survivin with siRNA potentiated the inhibitory effect of arsenic trioxide on proliferation in WSU-CLL cells. Also, knock-down of p53 by a specific siRNA prevented the down-regulation of survivin by arsenic trioxide and reduced the cytotoxic effect of arsenic trioxide to WSU-CLL cells. These results indicate that arsenic trioxide may be used to as novel therapeutic agent for chronic lymphocytic leukemia, which down-regulates survivin expression via a p53-dependent signaling pathway.