Inhibition of cell proliferation and the action mechanisms of arsenic trioxide (As2O3) on human breast cancer cells.
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 microM 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.
Chow
Stephanie K Y
SK
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
Chan
Judy Y W
JY
Fung
K P
KP
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D010087:Oxides / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation
D000970:Antineoplastic Agents; D001152:Arsenicals; D004273:DNA, Neoplasm; D010087:Oxides; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D000077237:Arsenic Trioxide