Glutaminase (PEG-PGA) increases antitumoral efficacy of cytotoxic agents. R. Harzmann, N. Esser, R. Loewe, J. Roberts, F. Leenders, W. Seifert, C. Unger, J. Drevs; Zentralklinikum Augsburg, Urologische Klinik, Augsburg, Bavaria, Germany; Albert-Ludwigs-University, Tumor Biology Center, Freiburg, Germany; Ludwig-Maximilian-University, Munich, Germany; University of South Carolina, Columbia, SC; celares GmbH, Berlin, Germany; University of Applied Sciences, Berlin, Germany Abstract: Background: Glutamine is essential for the survival of cancer cells. It is therefore a possible target for cancer therapy. Glutaminase (PEG-PGA) depletes the glutamine serum level and withdraws the supply of glutamine to the neoplastic cells. The tumor cells begin to either arrest in the cell cycle or enter apoptosis. This study investigated the combination of PEG-PGA with different cytotoxic agents in vitro and in vivo. Methods: Different cancer cell lines (HCT-15, HT29, SW-60, SF-539, A549, DMS-114, NCI-H23, NCI-H460, MCF7) were incubated with PEG-PGA and in addition perfused with different cytotoxic agents (6-Diazo-5-oxo-L-norleucine [DON], Actinomycin D, Mitomycin, Mitoxantrone, Cisplatin, Melphalan, Etoposid, 5FU,antracyclines, Paclitaxel and Tamoxifen). After fixation the cells were incubated with Sulfohodamin B and measured photometric at 575 nm absorption. In vivo, A549 cells were implanted subcutaneously into nude mice. Treatment was initiated after visible tumors had developed. Mice were treated with either PEG-PGA, DON, Cisplatin, the combination of DON and Cisplatin with PEG-PGA or vehicle. Tumor volumes and animal weights were taken every other day. Results: The combination of PEG-PGA with cytotoxic agents showed statistically significant increased activity in vitro. This finding could be confirmed by the in vivo study. Here, the combination of PEG-PGA and DON was more effective than the mono-therapy with DON. The efficacy of Cisplatin was synergistically increased by PEG-PGA as well, nevertheless, this finding was accompanied by an increase in toxicity. Conclusion: PEG-PGA is a promising new therapeutic reagent for the use in combination with cytotoxic agents to increase antitumoral efficacy. Therefore, PEG-PGA should enter phase I trials using cisplatin or other chemotherapeutics. Abstract No: 3183 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.