Journal article
The cationic small molecule GW4869 is cytotoxic to high phosphatidylserine-expressing myeloma cells
S Vuckovic, K Vandyke, DA Rickards, P McCauley Winter, SHJ Brown, TW Mitchell, J Liu, J Lu, PW Askenase, E Yuriev, B Capuano, PA Ramsland, GR Hill, ACW Zannettino, AT Hutchinson
British Journal of Haematology | WILEY | Published : 2017
DOI: 10.1111/bjh.14561
Abstract
We have discovered that a small cationic molecule, GW4869, is cytotoxic to a subset of myeloma cell lines and primary myeloma plasma cells. Biochemical analysis revealed that GW4869 binds to anionic phospholipids such as phosphatidylserine - a lipid normally confined to the intracellular side of the cell membrane. However, interestingly, phosphatidylserine was expressed on the surface of all myeloma cell lines tested (n = 12) and 9/15 primary myeloma samples. Notably, the level of phosphatidylserine expression correlated well with sensitivity to GW4869. Inhibition of cell surface phosphatidylserine exposure with brefeldin A resulted in resistance to GW4869. Finally, GW4869 was shown to delay..
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Awarded by National Cancer Institute
Funding Acknowledgements
This work was supported by a Cure Cancer Australia and Cancer Australia Priority Driven grant (#1050067). ATH was a recipient of a Chancellor's Postdoctoral Fellowship at the University of Technology, Sydney and a Fulbright Postdoctoral Fellowship at Yale University. KV was supported by a Mary Overton Early Career Research Fellowship (Royal Adelaide Hospital). GRH is a NHMRC Australia Fellow and QLD Health Senior Clinical Research Fellow.