Rui V. Simoes1,
Natalia Kruchevsky1, Inna Serganova2, Ellen Ackestaff1,
George Sukenick3, Ronald G. Blasberg2, 4,
Jason A. Koutcher1, 5
1Medical
Physics, Memorial Sloan Kettering Cancer Center, New York, NY, United States;
2Neurology, Memorial Sloan Kettering Cancer Center, New York, NY,
United States; 3NMR Core Facility, Memorial Sloan Kettering Cancer
Center, New York, NY, United States; 4Radiology, Memorial Sloan
Kettering Cancer Center, New York, NY, United States; 5Weill
Cornell Medical College, Cornell University, New York, NY, United States
Activation of mitochondrial aconitase (m-acon) is an early biochemical change during prostate cancer (PCa) development, leading to a shift from citrate-producing to a citrate-oxidizing malignant phenotype. Deferiprone (DFP), an iron chelator used in the clinic has been shown to impair aconitase activity and inhibit cell growth. We have studied the effects of DFP on TRAMP C2 cells. DFP induced a marked decrease in TRAMP C2 cell growth (IC50=49 M), affecting many metabolic parameters detected by 31P and 13C-MRS, and decreasing cellular oxygen consumption. Our results show the potential of DFP to inhibit PCa growth at clinically relevant doses.
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