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Inhibition of cell proliferation and the action mechanisms of arsenic trioxide (As 2 O 3 ) on human breast cancer cells
Author(s) -
Chow Stephanie K.Y.,
Chan Judy Y.W.,
Fung K.P.
Publication year - 2004
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20102
Subject(s) - arsenic trioxide , apoptosis , cell cycle , cell growth , cell cycle checkpoint , flow cytometry , chemistry , cancer research , downregulation and upregulation , dna fragmentation , cancer cell , cell , microbiology and biotechnology , cancer , biology , programmed cell death , medicine , biochemistry , gene
Arsenic trioxide (As 2 O 3 ) is one of the arsenic compounds found in nature. As 2 O 3 has recently been used to treat patients suffering from retinoic acid receptor (AML). It is of clinical interest to investigate whether As 2 O 3 is also effective in treating solid tumors. Here, we report that As 2 O 3 exhibited inhibitory effects on the proliferation of human breast cancer MCF‐7 cells in a dose‐ and time‐dependent manner. The 50% inhibitory concentration (IC 50 ) of As 2 O 3 in inhibiting proliferation of MCF‐7 cells were 8, 1.8, and 1.2 μM 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 As 2 O 3 exerted its action on MCF‐7 cells via apoptosis, whereas the result of flow cytometry also indicated that As 2 O 3 could induce mitochondrial mediated cell‐cycle arrest at G 1 phase. Further studies by Western blot analysis indicated that As 2 O 3 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 As 2 O 3 might also be a good candidate for treating breast cancer. © 2004 Wiley‐Liss, Inc.