Levels of phospholipid metabolites in breast cancer cells treated with antimitotic drugs: A P-31-magnetic resonance spectroscopy study

Magnetic resonance spectroscopy (,MRS) methods have provided valuable infor mation on cancer cell metabolism. In this study, we characterized the P-31- MR spectra of breast cancer cell lines exhibiting differences in hormonal r esponse, estrogen receptors (positive/negative), and metastatic potential. A correlation was made between the cytotoxic effect of antimitotic drugs an d changes in cell metabolism pattern. Because most anticancer drugs are mor e effective on proliferating cells, our study attempted to elucidate the me tabolic profile and specific metabolic changes associated with the effect o f anticancer drugs on proliferating breast cancer cell lines. Accordingly, for the P-31-MRS experiments, cells were embedded in Matrigel to preserve t heir proliferation profile and ability to absorb drugs. The MRS studies of untreated cells indicated that the levels of phosphodiesters and uridine di phosphosugar metabolites were significantly higher in estrogen receptor-pos itive and low metastatic potential cell lines. P-31-MRS observations reveal ed a correlation bet een the mode of action of anticancer drugs and the obs erved changes in cell metabolic profiles. When cells were treated with anti microtubule drugs (paclitaxel, vincristine, colchicine, nocodazole), but no t with methotrexate and doxorubicin, a profound elevation of intracellular glycerophosphorylcholine (GPC) was recorded that was not associated with ch anges in phospholipid composition of cell membrane. Remarkably, the rate of elevation of intracellular GPC was much faster in cell population synchron ized at G(2)-M compared with the unsynchronized cells. The steady-state lev el of GPC for paclitaxel-treated cells was reached after similar to4 h for synchronized cells and after similar to 24 h (approximate duration of one c ell cycle) for the unsynchronized ones. These observations may indicate a c orrelation between microtubule status and cellular phospholipid metabolism. This study demonstrates that 31P-MRS may have diagnostic value for treatme nt decisions of breast cancer and reveals new aspects of the mechanism of a ction of and microtubule drugs.