Carboxyamidotriazole inhibits proliferation of human breast cancer cells via G2/M cell cycle arrest and apoptosis

Caiying Ye, Lei Guo, Dechang Zhang
Department of Pharmacology, Inst. of Basic Med. Sci., Chinese Academy of Med. Sci., Beijing, China

Carboxyamidotriazole (CAI) has been shown to be able to induce growth inhibition and apoptosis in cancer cells. We demonstrate that CAI significantly inhibits proliferation of cultured MCF-7 human breast cancer cells in a dose-dependent manner with an IC50 of 26 μM. Reduced proliferation of MCF-7 cells in the presence of CAI correlated with accumulation of cells in G2/M phase and induction of apoptosis. A treatment of MCF-7 cells with 30 μM CAI caused a time-dependent decrease in the levels of proteins that regulate G2/M progression, including Cdk1, Cyclin B1, and Cdc25C. A simultaneous increase in the expression of p21 protein was observed. We also demonstrated a concurrent decrease of the mitochondrial membrane potential (ΔΨm), and down-regulation of anti-apoptotic protein Bcl-2. In conclusion, it seems reasonable to hypothesize that the anti-tumor effect of CAI in MCF-7 cells is based on G2/M cell cycle arrest and inducing apoptosis.