MRS Detection of Altered Choline Metabolism Following HSP90 Inhibition

Alissa Brandes¹, Chris S. Ward¹, Judy S. Hwang¹, Sabrina M. Ronen¹

Although most anticancer therapies cause a drop in PC levels,, treatment with the HSP90 inhibitor 17-AAG has been shown to have the unique consequence of increasing PC. Our study investigated the mechanism behind this observed increase by monitoring the uptake and metabolism of [1,2-13C]-choline in live cells and cells extracts using 1H, 31P and 13C MRS and performing assays on the activity of enzymes involved in choline metabolism. Our data indicate that the observed increase in PC levels in 17-AAG-treated cancer cells is due to an increase in the synthesis of PC from extracellular choline, along with increased breakdown of PtdCho via PLC.