Surfactin induces apoptosis and G(2)/M arrest in human breast cancer MCF-7 cells through cell cycle factor regulation.

Surfactin, purified from Bacillus subtilis natto TK-1, inhibited proliferation of human breast cancer MCF-7 cells in a dose- and time-dependent manner, with IC(50) at 24, 48, and 72 h of 82.6, 27.3, and 14.8 microM, respectively. Surfactin-induced cell death was considered to be apoptotic by observing the typical apoptotic morphological change by acridine orange/ethidium bromide staining and Transferase-mediated dUTP Nick End-labeling assay. [Ca(2+)]i measurement revealed that surfactin induced a sustained increase in concentration of intracellular [Ca(2+)]i. Flow cytometric analysis also demonstrated that surfactin caused time-dependent apoptosis of MCF-7 cells through cell arrest at G(2)/M phase. Western blot revealed that surfactin induced accumulation of the tumor suppressor p53 and cyclin kinase inhibitor p21(waf1/cip1), and inhibited the activity of the G(2)-specific kinase, cyclin B1/p34(cdc2). Based on our findings, surfactin inhibited proliferation in MCF-7 cells by inducing apoptosis and the elevation of [Ca(2+)]i may play an important role in the apoptosis. The mechanism which surfactin caused G(2)/M arrest seems to be through cell cycle factor regulation.