A survival kinase, Akt, is a downstream factor in the 
phosphatidylinositide-3'-kinase-dependent pathway, which mediates many 
biological responses including glucose uptake, protein synthesis and the 
regulation of proliferation and apoptosis, which is assumed to contribute to 
acquisition of malignant properties of human cancers. Here we find that an 
anti-tumor antibiotic, tetrocarcin A, directly induces apoptosis of human breast 
cancer cells. The apoptosis is accompanied by the activation of a proteolytic 
cascade of caspases including caspase-3 and -9, and concomitantly decreases 
phosphorylation of Akt, PDK1, and PTEN, a tumor suppressor that regulates the 
activity of Akt through the dephosphorylation of polyphosphoinositides. 
Tetrocarcin A affected neither expression of Akt, PDK1, or PTEN, nor did it 
affect the expression of Bcl family members including Bcl-2, Bcl-X(L), and Bax. 
These results suggest that tetrocarcin A could be a potent chemotherapeutic 
agent for human breast cancer targeting the phosphatidylinositide-3'-kinase/Akt 
signaling pathway.