Tautomycetin (TMC), originally isolated from Streptomyces griseochromogenes, has been suggested as a potential
drug retaining specificity toward
colorectal cancer. However, we found that TMC exhibited inhibitory effects on cell proliferation of many
cancer cell lines including
adriamycin-resistant human breast
adenocarcinoma. We investigated its anti-
tumor activity and mechanisms in human
breast cancer cells for the first time. In this study, we showed that TMC effectively inhibited
breast cancer cell proliferation, migration, and invasion. TMC also induced apoptosis in MCF-7 cells. This apoptotic response was in part mediated by Bcl-2 cleavage, leading to the release of
cytochrome c, which facilitates binding of Apaf-1 to
caspase-9 in its presence and subsequent activation of
caspase-7 in apoptosis induction signaling pathways. Furthermore, we identified that TMC induced apoptosis by suppressing Akt signaling pathway activation, which is independent of
protein phosphatase PP1 inhibition. The levels of downstream targets of Akt, including phospho-
forkhead transcription factor and Bad, were also reduced after TMC treatment. Overall, our results indicate that TMC could be used as a potential
drug candidate for
breast cancer therapy. More importantly, our study provides new mechanisms for the anticancer effects of TMC.