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Duramycin exhibits antiproliferative properties and induces apoptosis in tumour cells

Yates, Katherine R.a; Welsh, Jessicaa; Udegbunam, Nkeiruka O.a; Greenman, Johna; Maraveyas, Anthonyb; Madden, Leigh A.a

Blood Coagulation & Fibrinolysis: July 2012 - Volume 23 - Issue 5 - p 396–401
doi: 10.1097/MBC.0b013e3283538875
Original Articles

Duramycin is a polypeptide that binds specifically to phosphatidylethanolamine (PE) on cell surfaces with high affinity, and has been shown to disrupt tumour cell surface-based coagulation and exhibit weak antimicrobial activity. The aim of the present study was to characterize the effect of duramycin on tumour cell proliferation and viability. Duramycin was used to detect phosphatidylethanolamine expression on cell lines by flow cytometry. Cells were cultured in the presence of duramycin and proliferation and cell viability assessed. Electron microscopy and confocal microscopy were utilized to investigate cell membrane structure after duramycin treatment. Pancreatic tumour cells were shown to express phosphatidylethanolamine on their cell surfaces by specific labelling with duramycin. Phosphatidylethanolamine expression was generally increased in apoptotic cells and more so in necrotic cells. Cells cultured in the presence of duramycin showed increasing levels of apoptosis and ultimately necrosis with increasing duramycin concentrations, and cell proliferation was reduced in a duramycin dose-dependent manner between 0.125 and 12.5 μmol/l. Tissue factor expression was also reduced when cells were cultured in the presence of duramycin. Cells imaged by electron microscopy were fragile, suggesting that membrane integrity was compromised by duramycin, although no obvious differences in membrane structure were observed by live cell confocal imaging. Duramycin induced apoptosis and exhibited antiproliferative and anticoagulant effects on pancreatic tumour cells, most probably by disrupting cell membrane structure and/or function.

aPostgraduate Medical institute, University of Hull, Hull

bQueen's Centre for Oncology & Haematology, Castle Hill Hospital, Cottingham, UK

Correspondence to Leigh A. Madden, Room 003, Hardy Building, University of Hull, Hull, HU6 7RX, UK Tel: +44 1482 466031; fax: +44 1482 466031; e-mail: l.a.madden@hull.ac.uk

Received 20 January, 2012

Revised 8 March, 2012

Accepted 10 March, 2012

© 2012 Lippincott Williams & Wilkins, Inc.