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.
Cao
Xiaohong
X
Key Laboratory of Food Safety and Sanitation, Ministry of Education, College of food Engineering and Biotechnology, Tianjin University of Science and Technology, No. 29, 13th Avenue, Tianjin Economy Technological Development Area, Tianjin, 300457, China. wahwawayu@126.com
Wang
A H
AH
Jiao
R Z
RZ
Wang
C L
CL
Mao
D Z
DZ
Yan
L
L
Zeng
B
B
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D056744:Cyclin B1 / Q000187:drug effects / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D055666:Lipopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000494:pharmacology* / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D056744:Cyclin B1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D055666:Lipopeptides; D010456:Peptides, Cyclic; D016159:Tumor Suppressor Protein p53; C009365:surfactin peptide; D002118:Calcium