现代化学与应用

抽象的

The Effect of Arvanil on Prostate Cancer Cells Studied by Whole Cell High Resolution Magic Angle Spinning NMR

Wei Li and Bob M Moore II

The transient receptor potential cation channel subfamily V member 1 (TRPV1) has recently gained attention as a potential target for the development of novel antineoplastic agents. It has been reported that the TRPV1 agonist arvanil has effective antiproliferative effects in studies using human breast cancer cells lines. In an extension of this research we have evaluated the IC50 values of arvanil in the prostate cancer cell lines PPC-1 (primary) and TSU (metastatic). Both TSU and PPC-1 cell lines are sensitive to treatment with arvanil. This result prompted our investigations into the changes in “cell metabolism” associated with prostate cancer progression and the effect of arvanil treatment. To this end, we have employed High Resolution Magic-Angle Spinning (HR-MAS) NMR spectroscopy on whole cells to determine the differences in the relative amount of cell metabolites and changes in small molecule metabolism following treatment of the TSU and PPC-1 cells with arvanil. We evaluated and confirmed that the existing “biomarkers” such as elevated tCho and decreased citrate in prostate cancer are well correlated with prostate cancer progression. In addition, metastatic TSU cells also contain elevated level of lactate and glutamine, and contain much less creatine. Upon treatment with arvanil, a number of biomolecules were found to undergo changes in intracellular levels during apoptosis. These data will potentially permit the further characterization of signaling pathways associated with TRPV1 activation as well as identifying new targets for the development of novel antineoplastic agents.