Berners-Price S J, Sant M E, Christopherson R I, Kuchel P W
Department of Biochemistry, University of Sydney, New South Wales, Australia.
Magn Reson Med. 1991 Mar;18(1):142-58. doi: 10.1002/mrm.1910180115.
The effect of the antitumor complex [Au(dppe)2]Cl (where dppe is Ph2P(CH2)2PPh2) on the overall metabolism of cultured mouse L1210 leukemia cells was investigated by comparing 1H and 31P NMR spectra of perchloric acid extracts of cells incubated for 1 h in the presence and absence of 2 microM [Au(dppe)2]Cl. There were marked (ca. two-fold) increases in the levels of lactate and almost all detectable amino acids suggesting a drug-induced increase in the rate of glycolysis and inhibition of protein synthesis. The levels of taurine and phosphorylcholine were significantly decreased and 31P NMR spectra revealed a depletion of nucleoside triphosphates (NTP). The effect on nucleotide metabolism was investigated further by separating purine and pyrimidine nucleotides and precursors by anion-exchange HPLC. NTP levels were depleted by ca. 70-90% and there was a ca. three- to four-fold increase in nucleoside di- and monophosphates. The effect is postulated to be the result of uncoupling of mitochondrial oxidative phosphorylation. The Cu(I) complex [Cu(Ph2PCH = CHPPh2)2]Cl produced a similar effect on the cellular metabolism but was more potent. The water-soluble complex [Cu(Ph2P(CH2)PEt2)2]Cl caused the accumulation of cellular amino acids at a concentration that did not significantly deplete ATP levels.
通过比较在存在和不存在2微摩尔[Au(dppe)2]Cl的情况下培养1小时的细胞的高氯酸提取物的1H和31P NMR光谱，研究了抗肿瘤复合物[Au(dppe)2]Cl（其中dppe为Ph2P(CH2)2PPh2）对培养的小鼠L1210白血病细胞整体代谢的影响。乳酸和几乎所有可检测到的氨基酸水平显著增加（约两倍），表明药物诱导糖酵解速率增加并抑制蛋白质合成。牛磺酸和磷酸胆碱水平显著降低，31P NMR光谱显示核苷三磷酸（NTP）耗竭。通过阴离子交换HPLC分离嘌呤和嘧啶核苷酸及其前体，进一步研究了对核苷酸代谢的影响。NTP水平降低了约70 - 90%，核苷二磷酸和单磷酸增加了约三到四倍。推测这种作用是线粒体氧化磷酸化解偶联的结果。铜（I）配合物[Cu(Ph2PCH = CHPPh2)2]Cl对细胞代谢产生类似作用，但效力更强。水溶性配合物[Cu(Ph2P(CH2)PEt2)2]Cl在不显著消耗ATP水平的浓度下导致细胞氨基酸积累。
