Inhibition of cell proliferation and the action mechanisms of arsenic trioxide (As2O3) on human breast cancer cells

Arsenic trioxide(As2O3) is one of the arsenic compounds found in nature. As2O3 has recently been used to treat patients suffering from retinoic acid receptor (AML). It is of clinical interest to investigate whether As2O3 is also effective in treating solid tumors. Here, we report that As2O3 exhibited inhibitory effects on the proliferation of human breast cancer MCF-7 cells in a dose- and time-dependent manner. The 50% inhibitory concentration (IC50) of As2O3 in inhibiting proliferation of MCF-7 cells were 8, 1.8, and 1.2 muM upon 1-, 2-, and 3-day treatment, respectively. In elucidating the underlying action mechanisms, the results of experiments concerning DNA fragmentation and externalization indicated that As2O3 exerted its action on MCF-7 cells via apoptosis, whereas the result of flow cytometry also indicated that As2O3 could induce mitochondrial mediated cell-cycle arrest at G, phase. Further studies by Western blot analysis indicated that As2O3 regulated apoptosis and the expression of cell-cycle-related proteins as it upregulated p53 protein level and downregulated bcl-2 protein level. Results in present study indicated that As2O3 might also be a good candidate for treating breast cancer. (C) 2004 Wiley-Liss, Inc.