Surfactin Induces Apoptosis and G2/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 IC50 at 24, 48, and 72 h of 82.6, 27.3, and 14.8 μM, 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. [Ca2+]i measurement revealed that surfactin induced a sustained increase in concentration of intracellular [Ca2+]i. Flow cytometric analysis also demonstrated that surfactin caused time-dependent apoptosis of MCF-7 cells through cell arrest at G2/M phase. Western blot revealed that surfactin induced accumulation of the tumor suppressor p53 and cyclin kinase inhibitor p21waf1/cip1, and inhibited the activity of the G2-specific kinase, cyclin B1/p34cdc2. Based on our findings, surfactin inhibited proliferation in MCF-7 cells by inducing apoptosis and the elevation of [Ca2+]i may play an important role in the apoptosis. The mechanism which surfactin caused G2/M arrest seems to be through cell cycle factor regulation.