This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Beloueche-Babari, M. Articles by Ronen, S. M. Search for Related Content PubMed PubMed Citation Articles by Beloueche-Babari, M. Articles by Ronen, S. M.

¹ Cancer Research UK Clinical Magnetic Resonance Research Group, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust; ² Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey, United Kingdom

Requests for reprints: Mounia Beloueche-Babari, Cancer Research UK Clinical Magnetic Resonance Research Group, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT, United Kingdom. Phone: 44-208-661-3728; Fax: 44-208-661-0846. E-mail: Mounia.Beloueche-Babari{at}icr.ac.uk

Phosphoinositide 3-kinase (PI3K) is an attractive target for novel mechanism-based anticancer treatment. We used magnetic resonance (MR) spectroscopy (MRS) to detect biomarkers of PI3K signaling inhibition in human breast cancer cells. MDA-MB-231, MCF-7, and Hs578T cells were treated with the prototype PI3K inhibitor LY294002, and the ³¹P MR spectra of cell extracts were monitored. In every case, LY294002 treatment was associated with a significant decrease in phosphocholine levels by up to 2-fold (P < 0.05). In addition, a significant increase in glycerophosphocholine levels by up to 5-fold was also observed (P 0.05), whereas the content of glycerophosphoethanolamine, when detectable, did not change significantly. Nucleotide triphosphate levels did not change significantly in MCF-7 and MDA-MB-231 cells but decreased by 1.3-fold in Hs578T cells (P = 0.01). The changes in phosphocholine and glycerophosphocholine levels seen in cell extracts were also detectable in the ³¹P MR spectra of intact MDA-MB-231 cells following exposure to LY294002. When treated with another PI3K inhibitor, wortmannin, MDA-MB-231 cells also showed a significant decrease in phosphocholine content by 1.25-fold relative to the control (P < 0.05), whereas the levels of the remaining metabolites did not change significantly. Our results indicate that PI3K inhibition in human breast cancer cells by LY294002 and wortmannin is associated with a decrease in phosphocholine levels. [Mol Cancer Ther 2006;5(1):187–96]

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Note: P. Workman is a Cancer Research UK Life Fellow.

S.M. Ronen is currently at the Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4095.

Received 9/22/05; revised 10/17/05; accepted 11/ 4/05.